| 1. |
- Nylander, Ingrid, et al.
(author)
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A comparison of microwave irradiation and decapitation. Basal levels of dynorphin and enkephalin peptides and the effect of morphine treatment on dynorphin peptides
- 1997
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In: Neuropeptides. - 0143-4179 .- 1532-2785. ; 31:4, s. 357-365
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Journal article (peer-reviewed)abstract
- Opioid peptides were analysed in tissue extracts of various brain structures and the pituitary gland from rats sacrificed by microwave irradiation, and compared with peptide levels in tissue extracts from decapitated rats. Dynorphin A, dynorphin B and Leu-enkephalinArg6, derived from prodynorphin, and Met-enkephalinArg6Phe7 from proenkephalin, were measured. Basal immunoreactive levels of dynorphin A and B were consistently higher in extracts from microwave-irradiated rats, whereas in these extracts immunoreactive levels of Leu-enkephalinArg6, an endogenous metabolite of dynorphin peptides, were either lower than, the same as or higher than in decapitated rats. Immunoreactive levels of Met-enkephalinArg6Phe7 were higher in microwave-irradiated rats. Effects of morphine treatment on prodynorphin peptide levels were evaluated and compared with previous findings in decapitated rats. Dynorphin immunoreactive levels were higher in the nucleus accumbens and striatum of morphine-tolerant rats than in corresponding areas in saline-treated rats. These results indicate tissue-specific metabolism of prodynorphin peptides and show that metabolism of opioid peptides occurs during the dissection procedure after decapitation of the rat even though precautions are taken to minimize degradation.
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| 2. |
- Ploj, Karolina, et al.
(author)
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Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats
- 2003
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In: Neuropeptides. - 0143-4179 .- 1532-2785. ; 37:3, s. 149-156
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Journal article (peer-reviewed)abstract
- Environmental manipulations early in life may induce persistent alterations in adult behaviour and physiology. The underlying neural mechanisms of these responses are not yet clear. We have previously reported long-term changes in brain opioid peptide levels in male and female Sprague-Dawley rats after short periods (15 min, known as neonatal handling) of maternal separation (MS) until weaning. To study this further, we investigated behavioural and neurochemical effects of repeated MS in male Wistar rats. The rat pups were separated from their dams in litters for either 360 min (MS360) or 15 min (MS15) daily from postnatal day 1 to 21 or exposed to normal animal facility rearing. Behavioural analysis showed that MS360 rats had increased ultrasonic calls on postnatal day 5 compared to MS15 rats, but not on postnatal day 6. Moreover, the MS360 rats had more animals with higher frequency of calls at day 5 than 6 than the MS15 rats. Analysis of the opioid peptides dynorphin B and Met-enkephalin-Arg(6)Phe(7) with radioimmunoassay 7 weeks after the MS procedure, revealed long-term neurochemical changes in several brain areas and in the pituitary gland. Immunoreactive dynorphin B and Met-enkephalin-Arg(6)Phe(7) levels were affected in the hypothalamus and dynorphin B levels in the neurointermediate pituitary lobe, amygdala, substantia nigra and the periaqueductal gray. Together, these findings show that repeated periods of MS early in life in male Wistar rats affect the development of the ultrasonic call response and induce long-lasting and possibly permanent alterations in the opioid peptide systems.
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| 3. |
- Tan No, K, et al.
(author)
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Intrathecal administration of p-hydroxymercuribenzoate or phosphoramidon/bestatin-combined induces antinociceptive effects through different opioid mechanisms
- 1998
-
In: Neuropeptides. - 0143-4179 .- 1532-2785. ; 32:5, s. 411-415
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Journal article (peer-reviewed)abstract
- The antinociceptive effect of intrathecally (i.t.) administered protease inhibitors was tested against capsaicin (800 ng) injected into the dorsal surface of a hindpaw. Both p-hydroxymercuribenzoate (2-8 nmol), a cysteine protease inhibitor, and phosphoramidon (1-4 nmol), an endopeptidase 24.11 inhibitor in the presence of bestatin (0.25 nmol) an aminopeptidase inhibitor, administered i.t. 60 min prior to the injection of capsaicin produced a dose-dependent reduction of the capsaicin-induced paw licking and biting response. p-Hydroxymercuribenzoate (4 nmol)-induced antinociception was significantly antagonized by nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by naltrindole, a selective delta-opioid receptor antagonist. On the other hand, phosphoramidon (4 nmol) /bestatin-induced antinociception was significantly antagonized by naltrindole, but not by nor-binaltorphimine. The results indicate that the antinociceptive effect of p-hydroxymercuribenzoate may be due to the inhibition of a cysteine protease degrading endogenous dynorphins whereas phosphoramidon in the presence of bestatin blocks the degradation of enkephalins.
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| 4. |
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| 5. |
- Ali, M Al Haj, et al.
(author)
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Distribution of neuroendocrine cells in the small and large intestines of the one-humped camel (Camelus dromedarius)
- 2007
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 41:5, s. 293-299
-
Journal article (peer-reviewed)abstract
- The distribution and relative frequency of neuroendocrine cells in the small and large intestines of one-humped camel were studied using antisera against 5-hydroxytryptamine (5-HT), cholecystokinin (CCK-8), somatostatin (SOM), peptide tyrosine tyrosine (PYY), gastric inhibitory polypeptide (GIP), neuronal nitric oxide synthase (nNOS), gastrin releasing peptide (GRP), substance P (SP), and neurokinin A (NKA). Among these cell types, CCK-8 immunoreactive (IR) cells were uniformly distributed in the mucosa, while others showed varied distribution in the villi or crypts of the small intestine. Immunoreactive cells like 5HT, CCK-8, and SOM showed peak density in the villi and crypts of the small intestine and in the colonic glands of the large intestine, while cells containing SP were discerned predominately in the crypts. 5-HT, CCK-8 and SOM cells were mainly flask-shaped and of the open-variety, while PYY and SP immunoreactive cells were mainly rounded or basket-shaped and of the closed variety. Basically the distribution pattern of the endocrine cells in the duodenum, jejunum and colon of the one-humped camel is similar to that of other mammals. Finally, the distribution of these bioactive agents may give clues as to how these agents aid in the function of the intestinal tract of this desert animal.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Edoff, Karin, 1973-, et al.
(author)
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Neuropeptide effects on rat chondrocytes and perichondrial cells in vitro
- 2003
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 37:5, s. 316-318
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Journal article (peer-reviewed)abstract
- This study examines if cultured chondrocytes and perichondrial cells change the level of cAMP and/or cGMP in response to application of the neuropeptide calcitonin gene-related peptide (CGRP). Cells collected from the knee region of 4–8 days old rat pups were cultured in vitro. Cultures were exposed to 10−10–10−6 M CGRP during 10 minutes. The levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the cultures and in controls were determined by radioimmunoassay. The results show that application of CGRP causes a distinctly increased level of cAMP, that was absent when CGRP was applied together with the CGRP1 receptor antagonist. The level of cGMP was not obviously altered. Hence, it is possible that terminals of primary sensory neurones present in developing cartilage influence chondrocytes and perichondrial cells via local release of CGRP.
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| 10. |
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| 11. |
- Erdling, André, et al.
(author)
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VIP/PACAP receptors in cerebral arteries of rat: Characterization, localization and relation to intracellular calcium.
- 2013
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In: Neuropeptides. - : Elsevier BV. - 1532-2785 .- 0143-4179. ; 47:2, s. 85-92
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this study was to describe the effects of two putative VIP/PACAP receptor antagonists and the distribution of the receptor protein in rat brain vessels. METHODS: The vascular effects of VIP, PACAP-27 and PACAP-38 were investigated in segments of rat middle cerebral artery (MCA) by pressurized arteriography, and in a wire myograph. The antagonistic responses to PACAP6-38 and PG99-465 were evaluated. In addition, the receptor subtypes for VIP and PACAP (VPAC(1), VPAC(2) and PAC(1)) were visualized in the rat middle cerebral artery by immunohistochemistry and Western blotting. RESULTS: In the perfusion model, abluminal but not luminal VIP, PACAP-27 and PACAP-38 caused concentration-dependent relaxations of the MCA (27.1±0.2%, 25.2±0.4% and 0.3±0.1%, respectively). In the wire myograph, there was no significant difference in potency of the peptides in the MCA. In both systems, PACAP6-38 and PG99-465 inhibited the VIP induced relaxation. Western blot showed the presence of the receptor proteins in cerebral vasculature and immunohistochemistry showed that all three receptors are present and located in the cytoplasm of smooth muscle cells. CONCLUSION: In both systems, the two blockers antagonized the relaxant VIP effect; the potency order of agonists and the immunohistochemistry suggest the presence of the dilatory VPAC(1) and VPAC(2) receptors on the smooth muscle cells.
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| 12. |
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| 13. |
- Fransson, Rebecca, et al.
(author)
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Small peptides mimicking substance P (1-7) and encompassing a C-terminal amide functionality
- 2008
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:1, s. 31-37
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Journal article (peer-reviewed)abstract
- Some of the biological effects demonstrated after administration of substance P (SP) in vivo can indirectly be attributed to the fragmentation of the undecapeptide to its N-terminal bioactive fragment SP1–7. This heptapeptide (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) is a major bioactive metabolite from SP that frequently exerts similar biological effects as the parent peptide but also, in several cases, completely opposite actions. Specific binding sites for the heptapeptide SP1–7 that are separate from the SP preferred NK receptors have been identified. In this study we demonstrate that (a) the C-terminal part of the SP metabolite SP1–7 is most important for binding as deduced from an Ala scan and that a replacement of Phe7 for Ala is deleterious, (b) truncation of the N-terminal amino acid residues of SP1–7 delivers peptides with retained binding activity, although with somewhat lower binding affinities than SP1–7 and (c) a C-terminal amide group as a replacement for the terminal carboxy group of SP1–7 and for all of the truncated ligands synthesized affords approximately 5–10-fold improvements of the binding affinities.
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| 14. |
- Fällmar, Helena, 1980-, et al.
(author)
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Identification of positions in the human neuropeptide Y/peptide YY receptor Y2 that contribute to pharmacological differences between receptor subtypes
- 2011
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 45:4, s. 293-300
-
Journal article (peer-reviewed)abstract
- The members of the neuropeptide Y (NPY) family are key players in food-intake regulation. In humans this family consists of NPY, peptide YY (PYY) and pancreatic polypeptide (PP) which interact with distinct preference for the four receptors showing very low sequence identity, i.e. Y1, Y2, Y4 and Y5. The binding of similar peptides to these divergent receptors makes them highly interesting for mutagenesis studies. We present here a site-directed mutagenesis study of four amino acid positions in the human Y2 receptor. T(3.40) was selected based on sequence alignments both between subtypes and between species and G(2.68), L(4.60) and Q(6.55) also on previous binding studies of the corresponding positions in the Y1 receptor. The mutated receptors were characterized pharmacologically with the peptide agonists NPY, PYY, PYY(3-36), NPY(13-36) and the non-peptide antagonist BIIE0246. Interestingly, the affinity of NPY and PYY(3-36) increased for the mutants T(3.40)I and Q(6.55)A. Increased affinity was also observed for PYY to Q(6.55)A. PYY(3-36) displayed decreased affinity for G(2.68)N and L(4.60)A whereas binding of NPY(13-36) was unaffected by all mutations. The antagonist BIIE0246 showed decreased affinity for T(3.40)I, L(4.60)A and Q(6.55)A. Although all positions investigated were found important for interaction with at least one of the tested ligands the corresponding positions in hY1 seem to be of greater importance for ligand binding. Furthermore these data indicate that binding of the agonists and the antagonist differs in their points of interaction. The increase in the binding affinity observed may reflect an indirect effect caused by a conformational change of the receptor. These findings will help to improve the structural models of the human NPY receptors.
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| 15. |
- Grimsholm, Ola, et al.
(author)
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Observations favouring the occurrence of local production and marked effects of bombesin/gastrin-releasing peptide in the synovial tissue of the human knee joint : comparisons with substance P and the NK-1 receptor.
- 2008
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:2, s. 133-145
-
Journal article (peer-reviewed)abstract
- We have previously shown that levels of the neuropeptides substance P (SP) and bombesin/gastrin-releasing peptide (BN/GRP) in blood and synovial fluid correlate with levels of pro-inflammatory cytokines in patients with rheumatoid arthritis (RA). It is well-established that SP is present in nerve endings in the synovium whilst the source of BN/GRP in human joints is completely unknown. Nor is it known whether GRP-receptors (GRP-R) are present in human synovial tissue. This study aimed to investigate the expression pattern of SP, BN/GRP and their receptors (NK-1R and GRP-R) in synovial tissue. Synovial tissue specimens from patients with RA or osteoarthritis (OA) were processed for immunohistochemistry, in situ hybridisation and ELISA. The results show the presence of BN/GRP, but not SP, in cells in the synovial tissue at both the protein and mRNA level. We did not find immunoreactive BN/GRP in nerve structures. NK-1R and GRP-R were also expressed at both protein and mRNA levels in cells associated with blood vessels and cells in the interstitial tissue. ELISA analyses revealed both SP and BN/GRP to be present in synovial tissue extracts and that synovial levels of SP were higher in RA patients than those with OA. Our results indicate that BN/GRP is produced by non-neuronal cells in the synovial tissue. Furthermore, both BN/GRP and SP may exert their effects on the synovial tissue through the respective receptors. These results suggest that BN/GRP and SP may modulate inflammation and vascular events, and possibly healing processes in the synovium. Finally, nerves should not be considered as the source of BN/GRP in synovial tissue although this peptide is presumably intimately involved functionally in synovial tissue, a previously unrecognised fact.
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| 16. |
- Gustafsson, Lisa, et al.
(author)
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The impact of postnatal environment on opioid peptides in young and adult male Wistar rats
- 2008
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:2, s. 177-191
-
Journal article (peer-reviewed)abstract
- Early environmental influences can change the neuronal development and thereby affect behavior in adult life. The aim in the present study was to thoroughly examine the impact of early environmental factors on endogenous opioids by using a rodent maternal separation (MS) model. The endogenous opioid peptide system is not fully developed at birth, and short- and/or long-term alterations may occur in these neural networks in animals exposed to manipulation of the postnatal environment. Rat pups were subjected to one of five rearing conditions; 15 min (MS15) litter (l) or individual (i), 360 min (MS360) l or i daily MS, or housed under normal animal facility rearing (AFR) conditions during postnatal days 1-21. Measurements of immunoreactive (ir) Met-enkephalin-Arg(6)Phe(7) (MEAP) and dynorphin B (DYNB) peptide levels in the pituitary gland and in a number of brain areas, were performed at three and 10 weeks of age, respectively. MS-induced changes were more pronounced in ir MEAP levels, especially in individually separated rats at three weeks of age and in litter-separated rats at 10 weeks of age. The enkephalin and dynorphin systems have different developmental patterns, dynorphin appearing earlier, which may point at a more sensitive enkephalin system during the early postnatal weeks. The results provide evidence that opioid peptides are sensitive for early environmental factors and show that the separation conditions are critical and also result in changes manifesting at different time points. MS-induced effects were observed in areas related to stress, drug reward and dependence mechanisms. By describing effects on opioid peptides, the study addresses the possible role of a deranged endogenous opioid system in the previously described behavioral consequences of MS.
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| 17. |
- Hilke, Susanne, et al.
(author)
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Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17 beta-estradiol
- 2009
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In: NEUROPEPTIDES. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 43:4, s. 327-332
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Journal article (peer-reviewed)abstract
- Estrogen alters excitability and changes synaptic morphology in the rat hippocampal formation. We have compared, by means of radioimmunoassay and in situ hybridization, the effects of short-term treatment with 17 beta-estradiol on neuropeptide Y (NPY) in the brain of ovariectomized mice. A highly significant reduction in concentrations of NPY-like immunoreactivity (LI) was observed in the hippocampal formation, some cortical areas and the caudate nucleus 1 h after administration of 17 beta-estradiol as compared to the control group. In contrast, NPY transcript levels increased in the hippocampal formation (dentate gyrus) and the caudate nucleus, possibly representing a compensatory increase of NPY synthesis following increased estradiol-induced NPY release. These data suggest that 17 beta-estradiol, via membrane-related mechanisms, increases NPY release and synthesis in forebrain areas involved in cognition, mood and motor functions.
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| 18. |
- Holm, Lovisa, et al.
(author)
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Changes in galanin and GalR1 gene expression in discrete brain regions after transient occlusion of the middle cerebral artery in female rats
- 2012
-
In: Neuropeptides. - : Elsevier. - 0143-4179 .- 1532-2785. ; 46:1, s. 19-27
-
Journal article (peer-reviewed)abstract
- Injury to neurons results in upregulation of galanin in some central and peripheral systems, and it has been suggested that this neuropeptide may play a protective and trophic role, primarily mediated by galanin receptor 2 (GalR2). The objective of the present study was to investigate galanin, GalR1, GalR2 and GalR3 gene expression in the female rat brain seven days after a 60-min unilateral occlusion of the middle cerebral artery followed by reperfusion. Quantitative real-time PCR was employed in punch-biopsies from the locus coeruleus, somatosensory cortex and dorsal hippocampal formation including sham-operated rats as controls. Galanin gene expression showed a ~2.5-fold increase and GalR1 a ~1.5-fold increase in the locus coeruleus of the ischemic hemisphere compared to the control side. Furthermore, the GalR1 mRNA levels decreased by 35% in the cortex of the ischemic hemisphere. The present results indicate that a stroke-induced forebrain lesion upregulates synthesis of galanin and GalR1 in the locus coeruleus, a noradrenergic cell group projecting to many forebrain areas, including cortex and the hippocampal formation. These results support the notion that galanin may play a role in the response of the central nervous system to injury and have trophic eff ects.
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| 19. |
- Holm, Lovisa, et al.
(author)
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Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats
- 2011
-
In: Neuropeptides. - : Elsevier Science B.V., Amsterdam. - 0143-4179 .- 1532-2785. ; 45:1, s. 17-23
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Journal article (peer-reviewed)abstract
- Several studies have shown that injury to the central and peripheral nervous system can increase expression of galanin, a 29 amino acid neuropeptide. Moreover, there is evidence that galanin, especially through its galanin receptor 2 (GalR2) receptor, plays a neuroprotective role in different injury models. However, direct studies of a possible neuroprotective effect of galanin in experimental stroke models are lacking. Galanin, a GalR2/3 agonist or artificial CSF was continuously infused intracerebroventricularly (i.c.v.) in naive female rats after a 60 min transient and focal occlusion of the middle cerebral artery. The animals were sacrificed, and the ischemic lesion was visualized using 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The lesion was 98% larger after i.c.v, administration of the GalR2/3 agonist (2.4 nmol/day) seven days after occlusion compared to artificial CSF (p = 0.023). No statistically significant differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24 nmol/day; p = 0.939, 0.715 and 0.977, respectively). There was no difference in the size of the ischemic lesions measured after three days in the galanin-treated group (2.4 nmol/d) compared to artificial CSF (p = 0.925). The present results show, surprisingly, that a GalR2/3 agonist doubled the size of the ischemic lesion. Whether this effect primarily reflects the properties of the current model, species, gender and/or the mode of galanin administration, e.g. causing desensitization, or whether galanin indeed lacks neuroprotective effect of its own, remains to be corroborated.
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| 20. |
- Ihnatko, Robert, 1972-, et al.
(author)
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Short N-terminal galanin fragments are occurring naturally in vivo
- 2017
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In: Neuropeptides. - : Churchill Livingstone. - 0143-4179 .- 1532-2785. ; 63
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Journal article (peer-reviewed)abstract
- The galanin family currently consists of four peptides, namely galanin, galanin-message associated peptide, galanin-like peptide and alarin. Unlike galanin that signals through three different G protein-coupled receptors; GALL, GAL(2), and GAL(3), binding at its N-terminal end, the cognate receptors for other members of the galanin family are currently unknown. Research using short N-terminal galanin fragments generated either by enzymatic cleavage or solid-phase synthesis has revealed differences in their receptor binding properties exerting numerous biological effects distinct from galanin(1-29) itself. Our studies on tissue extracts derived from rat small intestine and bovine gut using chromatographic techniques and sensitive galanin(1-16)-specific radioimmunoassay revealed the presence of immunoreactive compounds reacting with antiserum against galanin(1-16) distributed in distinct elution volumes. These results suggested a possible presence of short N-terminal galanin fragments also in vivo. Moreover, employing immunoaffinity chromatography and reverse-phase high performance liquid chromatography (HPLC) followed by mass spectrometry allowed specific enrichment of these immunoreactive compounds from rat tissues and identification of their molecular structure. Indeed, our study revealed presence of several distinct short N-terminal galanin sequences in rat tissue. To prove their receptor binding, four of the identified sequences were synthetized, namely, galanin(1-13), galanin(1-16), galanin(1.20), galanin(6-20), and tested on coronal rat brain sections competing with I-125-labeled galanin(1-29). Our autoradiographs confirmed that galanin(1-13), galanin(1-16), and galanin(1-20) comprehensively displaced I-125-galanin(1-29) but galanin (6-20) did not. Here we show, for the first time, that short N-terminal galanin fragments occur naturally in rat tissues and that similar or identical galanin sequences can be present also in tissues of other species. Biological significance: This study is first to provide an evidence of the presence of short N-terminal galanin fragments in vivo in a biological system and provides further foundations for the previous studies using synthetized short N-terminal galanin fragments.
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| 21. |
- Jakobsson, Jon E. T., et al.
(author)
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Neuropeptide Y in itch regulation
- 2019
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In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 78
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Research review (peer-reviewed)abstract
- Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the threat. Itch-inducing (pruritogenic) substances activate primary afferent neurons in the skin through interactions with specific receptors that converts the stimulus into an electrical signal. These signals are conveyed to the dorsal horn of the spinal cord through the release of neurotransmitters such as natriuretic polypeptide b and somatostatin, leading to an integrated response within a complex spinal inteneuronal network. A large sub-population of somatostatin-expressing spinal interneurons also carry the Neuropeptide Y (NPY) Y1 receptor, indicating that NPY and somatostatin partly regulate the same neuronal pathway. This review focuses on recent findings regarding the role of the NPY/Y1 and somatostatin/SST2A receptor in itch, and also presents data integrating the two neurotransmitter systems.
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| 22. |
- Kilk, Kalle, et al.
(author)
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Targeting of antisense PNA oligomers to human galanin receptor type 1 mRNA
- 2004
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In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 38:5, s. 316-324
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Journal article (peer-reviewed)abstract
- In this work, we have targeted positions 18–38 of the human galanin receptor type 1 (GalR1) mRNA coding sequence with different peptide nucleic acid (PNA) oligomers. This region has previously been shown to be a good antisense region and therefore we aimed to identify the subregions and/or thermodynamic parameters determining the antisense efficacy. Nine different PNA oligomers were conjugated to a cell-penetrating peptide, transportan, to enhance their cellular uptake. Concentration-dependent down-regulation of GalR1 protein expression in human melanoma cell line Bowes was measured by radioligand binding assay. No reduction of GalR1 mRNA level was observed upon PNA treatment, thus, the effect was concluded to be translational arrest. Judging from the EC50 values, antisense PNA oligomers targeting regions 24–38 (EC50 = 70 nM) or 27–38 (EC50 = 80 nM) were the most potent suppressors of protein expression. No parameter predicted by M-fold algorithm was found to correlate with the measured antisense activities. Presence of some subregions was found not to increase antisense efficiency of PNA. Presence of a short unpaired triplet between nucleotides 33 and 35 in the target region was, on the other hand, found to be the most critical for efficient GalR1 down-regulation. Thus, the results are of high impact in designing antisense oligomers. Specific results of this study demonstrate 20-fold more efficient antisense down-regulation of GalR1 as achieved before.
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| 23. |
- Kuteeva, E, et al.
(author)
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Distribution of galanin in the brain of a galanin-overexpressing transgenic mouse
- 2005
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 39:3, s. 293-298
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Journal article (peer-reviewed)abstract
- The distribution of galanin mRNA-expressing cells and galanin-immuno reactive (I R) cell bodies and processes was studied in the brain of mice overexpressing galanin under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in colchicine-treated and non-treated animals. A widespread ectopic expression of galanin (both mRNA and peptide) was found, that is when neither transcript nor peptide could be seen in WT mice, not even after colchicine treatment. However, in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal cells, and Purkinje cells only galanin mRNA could be detected. The highest levels of galanin expression were observed in the Forebrain structures (the mitral cells of the olfactory bulb, throughout the cortex, granular and pyramidal cell layers of the hippocampus), in the mesencephalon (nucleus ruber), in the cerebellum (lateral cerebellar nucleus), in the pons (sensory and motor nuclei of the trigeminal nerve), within the medulla oblongata (facial, prepositus and spinal trigeminal nuclei). High densities of galanin-IR fibers were found in the axonal terminals of the lateral olfactory tract, hippocampal and presumably cerebellar mossy fiber system, in several thalamic and hypothalamic regions and the lower brain stem. (c) 2005 Elsevier Ltd. All rights reserved.
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| 24. |
- Lindahl, Andreas E, et al.
(author)
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Plasma chromogranin A after severe burn trauma
- 2013
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In: Neuropeptides. - : Elsevier. - 0143-4179 .- 1532-2785. ; 47:3, s. 207-212
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Journal article (peer-reviewed)abstract
- Background: Chromogranin A (CgA) in plasma (P-CgA), a neuroendocrine marker of sympathetic stress, has been shown to predict mortality in medical intensive care. We hypothesized that the magnitude of CgA release would reflect stress load, and thereby injury severity in burn intensive care patients. Methods: Fifty-one consecutive patients with a burn area exceeding 10% were included. P-CgA was measured twice daily for seven days after injury. The point value at 24 h, the mean and maximum values and the AUC at days 1-7, were tested as possible predictors. Injury severity in the form of organ dysfunction was measured as SOFA score at day 7. Results: P-CgA could be classified into two types with respect to variability over time. Patients with high variability had more deep injuries and were older than those with low variability. All measures of CgA correlated with SOFA score at day 7, but not with total burn size. Univariate regressions showed that age, burn size and three of four measures of P-CgA predicted organ dysfunction. Multiple regressions showed that age, burn size, and either P-CgA at 24 h, the mean value up to day 7, or the maximum value up to day 7, were independent predictors for organ dysfunction. Significant organ dysfunction was best predicted by age, burn area and the CgA point value at 24 h with an AUC value of 0.91 in a ROC-analysis. Conclusions: The extent of neuroendocrine activation assessed as P-CgA after a major burn injury is independently related to organ dysfunction.
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| 25. |
- Lundberg, Kristina, 1978-, et al.
(author)
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Diurnal and seasonal variation of cholecystokinin peptides in humans
- 2007
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In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 41:1, s. 59-63
-
Journal article (peer-reviewed)abstract
- Cholecystokinin (CCK) was determined in plasma obtained from 10 female (aged 23.4 ± SD 2.3 years) and nine male (aged 22.0 ± SD 1.4 years) healthy volunteers. Blood samples were drawn three times (8.00 a.m., 12 noon and 8.00 a.m.) on each of two sessions, one in the winter (November-December) and one in the summer (April-July). The participants had fasted (and were nicotine-free) since midnight preceding the sampling. A standardized breakfast was served after the first sampling. CCK was determined by radioimmunoassay. The area under the curve 0-24 h (AUC)CCK Winter was lower than AUCCCK Summer (F1:17 = 4.73, P = 0.0440) in the whole group of volunteers. On comparing the CCK concentrations within each session, there was an overall difference in winter (F2:36 = 14.81, P < 0.0001) as well in summer (F2:36 = 18.39, P < 0.0001). Post hoc comparisons yielded a difference between the 8.00 a.m. and 12 noon concentrations on the first day in winter (t = -3.96, P = 0.0009) as well as in summer (t = -4.64, P = 0.0002). The difference between the summer and winter AUCsCCK correlated with the difference between AUCs for temperatures in summer and winter (r = 0.58, P = 0.0089). The correlation was accounted for by the females (r = 0.73, P = 0.0171). The results are in accord with a diurnal and a seasonal variation of CCK in human plasma. © 2006 Elsevier Ltd. All rights reserved.
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| 26. |
- Lundström, Linda, et al.
(author)
-
Important pharmacophores for binding to galanin receptor 2
- 2005
-
In: Neuropeptides. - 0143-4179 .- 1532-2785. ; 39:3, s. 169-171
-
Journal article (peer-reviewed)abstract
- Galanin(2–11) has been introduced as a receptor subtype selective ligand for the GalR2 subtype of the galanin receptors, and has gained use in pharmacological studies of galaninergic signaling in the past two years. By introducing l-Ala substitutions in the galanin(2–11) sequence, we have examined the amino acid residues which are of importance for binding to the GalR2 receptor. Our study shows that Trp2, Asn5, Gly8 and Tyr9 are of great importance for high affinity binding. When placed in an α-helical conformation, the side chains of these residues are, with the exception of Tyr9, displayed on the same “side” of the peptide. This information is useful in the rational design of non-peptide type GalR2 receptor ligands.
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| 27. |
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| 28. |
- Löfgren, Magnus, 1979-, et al.
(author)
-
The additive effect of allopregnanolone on ghrelin's orexigenic effect in rats
- 2019
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 76
-
Journal article (peer-reviewed)abstract
- The progesterone metabolite, allopregnanolone (AlloP), is a GABA(A) receptor modulating steroid and is known to have orexigenic and pro-obesity effects. The neurobiological mechanisms underpinning these effects are most likely due to enhanced GABAergic signaling in the lateral arcuate nucleus (ARC) and medial paraventricular nucleus (PVN) of the hypothalamus. Inspired by the finding that GABAergic signaling is also important for the orexigenic effects of the circulating hormone, ghrelin, we sought to determine the extent to which AlloP (one of the most potent endogenous GABA(A)-receptor modulators) operates alongside ghrelin to enhance food intake. Male rats with ad libitum access to standard chow were injected intravenously with AlloP and/or ghrelin, alone or in combination. The intake of the standard chow was greater after AlloP 1 mg/kg together with ghrelin 30 mu g/kg than with 30 mu g/kg ghrelin alone. Food intake was also increased for the combined treatment of AlloP 0.5 mg/kg + ghrelin 10 mu g/kg, AlloP 1 mg/kg + ghrelin 10 mu g/kg, and AlloP 0.5 mg/kg + ghrelin 30 mu g/kg. There was no significant difference in food intake between the two ghrelin doses or between the two doses of AlloP and the vehicle. In electrophysiological studies, physiologically relevant concentrations of AlloP prolonged the current decay time of spontaneous inhibitory post-synaptic current of dissociated cells of the ARC and PVN. We conclude that AlloP enhances the hyperphagic effect of ghrelin, findings of potential relevance for the hyperphagia associated with the luteal phase of the reproductive cycle.
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| 29. |
- Magnusson, Kristina, et al.
(author)
-
Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography
- 2009
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 43:2, s. 105-111
-
Journal article (peer-reviewed)abstract
- The kappa opioid receptor ligand [(3)H]CI-977 was used to autoradiographically determine the density of kappa opioid receptors in the male rat brain following chronic treatment with the anabolic androgenic steroid nandrolone decanoate at two different doses. As compared to controls, significantly lower densities of the kappa opioid receptor were encountered after two weeks of high dose nandrolone decanoate (15 mg/kg) in the nucleus accumbens shell (16%), lateral hypothalamic area (36%), ventromedial hypothalamic nucleus (37%), dorsomedial hypothalamic nucleus (49%), central amygdaloid nucleus, capsular part (28%), lateral globus pallidus (35%) and in the stria terminalis (24%). Furthermore, an up-regulation of the receptor level was observed in the caudate putamen (18%) and in the dorsal endopiriform nucleus (23%). These alterations in the kappa opioid receptor expression are possibly attributed to a previously observed pronounced impact of nandrolone decanoate on the dynorphinergic system and could also include involvement of the dopaminergic reward system.
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| 30. |
- Mikrouli, Elli, et al.
(author)
-
Increased numbers of orexin/hypocretin neurons in a genetic rat depression model.
- 2011
-
In: Neuropeptides. - : Elsevier BV. - 1532-2785 .- 0143-4179. ; 45, s. 401-406
-
Journal article (peer-reviewed)abstract
- The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin-concentrating hormone (MCH) and cocaine and amphetamine regulated transcript (CART), that are involved in the regulation of both energy metabolism and sleep, have recently been implicated also in depression. We therefore hypothesized that alterations in these neuropeptide systems may play a role in the development of the FSL phenotype with both depressive like behavior, metabolic abnormalities and sleep disturbances. In this study, we first confirmed that the FSL rats displayed increased immobility in the Porsolt forced swim test compared to their control strain, the Flinders Resistant Line (FRL), which is indicative of depressive-like behavior. We then examined the number of orexin-, MCH- and CART-immunopositive neurons in the hypothalamus using stereological analyses. We found that the total number of orexin-positive neurons was higher in the hypothalamus of female FSL rats compared to female FRL rats, whereas no changes in the MCH or CART populations could be detected between the strains. Chronic treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram reduced immobility only in the FRL rats where it also increased the number of MCH positive neurons compared to untreated rats. These findings support the view that orexin may be involved in depression and strengthen the notion that the "depressed" brain responds differently to pharmacological interventions than the normal brain.
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| 31. |
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| 32. |
- Olesen, M. V., et al.
(author)
-
Y5 neuropeptide Y receptor overexpression in mice neither affects anxiety- and depression-like behaviours nor seizures but confers moderate hyperactivity
- 2012
-
In: Neuropeptides. - : Elsevier BV. - 1532-2785 .- 0143-4179. ; 46:2, s. 71-79
-
Journal article (peer-reviewed)abstract
- Neuropeptide Y (NPY) has been implicated in anxiolytic- and antidepressant-like behaviour as well as seizure-suppressant effects in rodents. Although these effects appear to be predominantly mediated via other NPY receptors (Y1 and/or Y2), several studies have also indicated a role for Y5 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY, Y1 or Y2 receptors in the hippocampus or amygdala has previously been shown to modulate emotional behaviour and seizures in rodents. The present study explored the potential effects of gene therapy with the Y5 receptor, by testing effects of recombinant adeno-associated viral vector (rAAV) encoding Y5 (rAAV-Y5) in anxiety- and depression-like behaviour as well as in kainate-induced seizures in adult mice. The rAAV-Y5 vector injected into the hippocampus and amygdala induced a pronounced and sustained increase in Y5 receptor mRNA expression and functional Y5 receptor binding, but no significant effects were found with regard to anxiety- and depression-like behaviours or seizure susceptibility. Instead, rAAV-mediated Y5 receptor transgene overexpression resulted in moderate hyperactivity in the open field test. These results do not support a potential role for single transgene overexpression of Y5 receptors for modulating anxiety-/depression-like behaviours or seizures in adult mice. Whether the induction of hyperactivity by rAAV-Y5 could be relevant for other conditions remains to be studied. (C) 2012 Elsevier Ltd. All rights reserved.
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| 33. |
- Oreland, Sadia, et al.
(author)
-
Short- and long-term consequences of different early environmental conditions on central immunoreactive oxytocin and arginine vasopressin levels in male rats
- 2010
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 44:5, s. 391-398
-
Journal article (peer-reviewed)abstract
- Numerous studies have provided evidence for an important role for the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in establishment of social behaviour early in life, such as mother-pup interactions. However, there are few reports examining the consequences of early-life experiences on OT and AVP in male offspring. We have used the maternal separation (MS) model to study the effect of different early environmental conditions in rats. The purpose was to study OT and AVP in rats subjected to prolonged daily MS (360 min, MS360), short daily MS (15 min, MS15) and conventional animal facility rearing (AFR) during postnatal days 1-21. In addition, the influence of the presence or absence of littermates during MS, i.e. litter-wise (l) or individual (i) MS, was assessed. The immunoreactive (ir) peptide levels were measured in the hypothalamus, amygdala and pituitary gland of 3 and 10 weeks old male rats. Assessment in 3-week-old rats revealed that MS15 was associated with low ir OT levels in the hypothalamus and amygdala and high levels in the pituitary gland compared with the MS360 and AFR condition. In the amygdala, differences between groups were also detected in adulthood. MS studies commonly use either MS15 or AFR as a control for prolonged MS. The present results show differences in MS360 rats as compared to MS15 but not AFR rats. Consequently, comparisons between prolonged MS with either short periods of MS or AFR will generate divergent results, hence, making the outcome of MS difficult to compare between studies. Moreover, the different early environments had no effect on ir AVP levels. In conclusion, OT in the amygdala was most sensitive to MS. Besides both short- and long-term consequences, distinct effects were seen after litter and individual separation, respectively. We propose that environmentally induced alterations in OT transmission due to disrupted mother-pup interactions early in life may cause altered susceptibility to challenges later in life.
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| 34. |
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| 35. |
- Ploj, Karolina, et al.
(author)
-
Neonatal handling in rats induces long-term effects on dynorphin peptides
- 1999
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 33:6, s. 468-474
-
Journal article (peer-reviewed)abstract
- The effects of neonatal handling on the opioid dynorphin peptides in the brain and pituitary gland of Sprague-Dawley rats were investigated. Ten weeks after the neonatal handling, handled rats had higher tissue levels of dynorphin A and B in the hypothalamus, pituitary gland and striatum and slightly higher dynorphin B levels in the hippocampus, medulla oblongata and midbrain as compared with non-handled controls. The results indicate a persistent upregulation of the dynorphin system in certain brain areas after neonatal handling, which could contribute to the behavioural changes in these rats observed later in life. Observation in the open field and the elevated plus-maze tests confirmed behavioural effects of neonatal handling, i.e. showing that handled rats exhibit attenuated fearfulness in novel environments as compared with non-handled rats.
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| 36. |
- Roman, Erika, et al.
(author)
-
Variations in opioid peptide levels during the estrous cycle in Sprague-Dawley rats
- 2006
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 40:3, s. 195-206
-
Journal article (peer-reviewed)abstract
- The estrous cycle, with its various hormonal conditions, may provide us with the means of understanding how endocrine states relate to opioid mechanisms. There has been increasing experimental support for interaction between sex steroids and opioid peptides in the central nervous system. Here, we describe fluctuations in endogenous brain immunoreactive (ir) peptide levels during various phases of the estrous cycle in the female Sprague-Dawley rat. Ir levels of dynorphin A, dynorphin B, Leu-enkephalin-Arg(6), Met-enkephalin-Arg(6)Phe(7) and nociceptin/orphanin FQ were measured in the pituitary gland and in 10 areas of the brain during the diestrus, proestrus and estrus phase. In several areas of the brain, basal levels of endogenous opioid peptides showed variation during the course of the estrous cycle. Significant differences were found between the diestrus state and the proestrus and/or estrus conditions, particularly in the nucleus accumbens, caudate putamen and the substantia nigra. The ir levels of the endogenous peptide nociceptin/orphanin FQ became altered in only one of the areas measured, indicating less variance during the estrous cycle. Correlation analyses revealed that significant associations between dynorphin A or dynorphin B and Leu-enkephalin-Arg(6) were found more often during estrus than during the diestrus and proestrus conditions. The ratio between the ir levels of Leu-enkephalin-Arg(6), a cleavage product of the enzymatic conversion of dynorphin peptides into shorter peptides in vivo, and dynorphin peptides was calculated. The significantly lower ratio between Leu-enkephalin-Arg(6) and dynorphin B in diestrus than in proestrus and estrus also indicates cyclic fluctuations in the enzymatic cleavage of dynorphin. These findings are discussed in relation to the possible role of interactions between sex steroids and opioid peptide mechanisms during the normal estrous cycle.
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| 37. |
- Runesson, Johan, 1980-, et al.
(author)
-
A novel GalR2-specific peptide agonist
- 2009
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 43:3, s. 187-192
-
Journal article (peer-reviewed)abstract
- The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 [(RG)(2)-N-galanin(2-13)-VL-(P)(3)-(AL)(2)-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target.
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| 38. |
- Samuelsson, Martin, et al.
(author)
-
Glutathione in the blood and cerebrospinal fluid: A study in healthy male volunteers
- 2011
-
In: Neuropeptides. - : Elsevier. - 0143-4179 .- 1532-2785. ; 45:4, s. 287-292
-
Journal article (peer-reviewed)abstract
- Glutathione (GSH) is an important regulator of intracellular redox homeostasis. In the brain, glutathione is considered a major antioxidant, which is also found at high concentrations in the extracellular environment. Altered GSH balance in plasma, blood and cerebrospinal fluid (CSF) has been observed in several disorders suggesting that an impaired antioxidant function is part of the pathophysiology. The aim of the present study was to investigate a possible relationship between glutathione in plasma and CSF. Blood samples were collected from 26 healthy male volunteers at 8 a.m., noon, 4 p.m. and 8 p.m. At 8 a.m. the following morning, blood was drawn and three 6-ml fractions of CSF were collected by lumbar puncture. In CSF, a disrupted gradient was found showing the highest glutathione concentration in the second compared to the first and third fraction (P andlt; 0.002). Moreover, correlation and regression analyses between glutathione in plasma and CSF revealed an association between the third fraction CSF and plasma glutathione 8 p.m. the day before lumbar puncture. Thus, if carefully standardised due to the disrupted gradient in CSF, it might be possible to estimate glutathione levels in CSF by analysing plasma in healthy males.
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| 39. |
- Sandor, Katalin, et al.
(author)
-
Spinal injection of newly identified cerebellin-1 and cerebellin-2 peptides induce mechanical hypersensitivity in mice
- 2018
-
In: Neuropeptides. - : CHURCHILL LIVINGSTONE. - 0143-4179 .- 1532-2785. ; 69, s. 53-59
-
Journal article (peer-reviewed)abstract
- By screening for neuropeptides in the mouse spinal cord using mass spectrometry (MS), we have previously demonstrated that one of the 78 peptides that is expressed predominantly (> 6-fold) in the dorsal horn compared to the ventral spinal cord is the atypical peptide desCER [des-Serl]-cerebellin, which originates from the precursor protein cerebellin 1 (CBLN1). Furthermore, we found that intrathecal injection of desCER induces mechanical hypersensitivity in a dose dependent manner. The current study was designed to further investigate the relative expression of other CBLN derived peptides in the spinal cord and to examine whether they share similar nociceptive properties. In addition to the peptides cerebellin (CER) and desCER we identified and relatively quantified nine novel peptides originating from cerebellin precursor proteins CBLN1 (two peptides), CBLN2 (three peptides) and CBLN4 (four peptides). Ten out of eleven peptides displayed statistically significantly (p < 0.05) higher expression levels (200-350%) in the dorsal horn compared to the ventral horn. Intrathecal injection of three of the four CBLN1 and two of the three CBLN2 derived peptides induced mechanical hypersensitivity in response to von Frey filament testing in mice during the first 6 h post-injection compared to saline injected mice, while none of the four CBLN4 derived peptides altered withdrawal thresholds. This study demonstrates that high performance MS is an effective tool for detecting novel neuropeptides in CNS tissues. We show the presence of nine novel atypical peptides originating from CBLN1, CBLN2 and CBLN4 precursor proteins in the mouse dorsal horn, whereof five peptides induce pain-like behavior upon intrathecal injection. Further studies are required to investigate the mechanisms by which CBLN1 and CBLN2 derived peptides facilitate nociceptive signal transmission.
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| 40. |
- Shebanits, Kateryna, et al.
(author)
-
Functional characterization in vitro of twelve naturally occurring variants of the human pancreatic polypeptide receptor NPY4R
- 2019
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 76
-
Journal article (peer-reviewed)abstract
- Obesity has become a global health problem and therefore understanding of the mechanisms regulating hunger and satiety is of utmost importance for the development of new treatment strategies. The Y4 receptor, encoded by the NPY4R gene, and its ligand pancreatic polypeptide (PP) have been reported to mediate a satiety signal. Multiple genetic studies have reported an association between NPY4R copy number and body weight. The gene also displays several SNP variants, many of which lead to amino acid differences, making it interesting to study. We have investigated the functional properties of 12 naturally occurring amino acid sequence variants of the Y4 and interpret the results in relation to sequence conservation and our structural model of the human Y4 receptor protein. Three receptor variants, Cys201ECL2Tyr, Val2716.41Leu and Asn3187.49Asp, were found to completely lose functional response, measured as inositol phosphate turnover, while retaining membrane expression. They display high sequence conservation and have important roles in the receptor structure. For two receptor variants the potency of PP was significantly decreased, Cys34NTSer (EC50 = 2.9 nM, p < .001) and Val1353.46Met (EC50 = 3.0 nM, p < .01), compared to wild-type Y4 (EC50 = 0.68 nM). Cys34 forms a disulphide bond with Cys298, linking the N-terminal part to ECL3. The Val1353.46Met variant has an amino acid replacement located in the TM3 helix, one helix turn above the highly conserved ERH motif. This position has influence on the network of residues involved in receptor activation and subsequent inactivation. Sequence conservation and the structural model are consistent with these results. The remaining seven positions had no significant effect on the receptor's functional response compared to wild-type Y4. These positions display more variation during evolution. Understanding of the interactions between the Y4 receptor and its native PP agonist and the effects of amino acid variation on its functional response will hopefully lead to future therapeutic possibilities.
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| 41. |
- Slawecki, Craig J., et al.
(author)
-
Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence : relation to anxiety-like and depressive-like behavior
- 2005
-
In: Neuropeptides. - : Elsevier. - 0143-4179 .- 1532-2785. ; 39:4, s. 369-377
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Recently, animal models have been developed that demonstrate that adolescent nicotine exposure produces neurobehavioral changes which persist into adulthood. This study further examined the impact of adolescent nicotine exposure on anxiety-like and depressive-like behavior, as well as on levels of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) in this model.METHODS: Male adolescent rats (35-40 days old) were administered nicotine using Nicoderm CQ patches (Smith-Kline Beecham). Behavior in the elevated plus maze (EPM) and forced swim test (FST) was assessed 2-3 weeks after exposure ended. Brain levels of CRF and NPY were then assessed 5-6 weeks after behavioral tests were completed. In addition, blood and brain levels of nicotine resulting from nicotine treatment were examined.RESULTS: After 5 days of exposure to 5 mg/kg/day nicotine, blood levels of nicotine averaged 66+/-5 ng/ml and brain nicotine levels averaged 52+/-4 ng/g. Rats exposed to nicotine displayed an anxiety-like profile in the EPM (i.e., decreased time spent in the open arms) and an antidepressant-like profile in the FST (i.e., less time spent immobile). Rats exposed to nicotine also had increased hypothalamic and frontal cortical CRF, increased hypothalamic and hippocampal NPY, and a decreased ratio of NPY to CRF in the amygdala.CONCLUSIONS: This study demonstrates that adolescent nicotine exposure produces lasting increases in anxiety-like behavior and may reduce depressive-like behavior. These behavioral changes also occurred in concert with alterations in CRF and NPY systems. Thus, lasting neurobehavioral changes associated with adolescent nicotine exposure may be related to allostatic changes in stress peptide systems.
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| 42. |
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| 43. |
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| 44. |
- Theodorsson, Annette, 1958-, et al.
(author)
-
Hypothermia-induced increase in galanin concentrations and ischemic neuroprotection in the rat brain
- 2008
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:1, s. 79-87
-
Journal article (peer-reviewed)abstract
- The effects of hypothermia on galanin concentrations and the relation between ischemic brain lesions, hypothermia and galanin concentrations in a transient and focal rat stroke model were investigated in order to elucidate whether hypothermia-induced alterations in galanin concentrations could constitute a part of the established neuroprotective effect of hypothermia. Female rats were allocated to normothermia (37 °C) or hypothermia (33 °C) treatments during a 60 min microclip middle cerebral artery occlusion. The ischemic lesions were visualized after observation periods of 2 or 7 days and the concentration of galanin measured by radioimmunoassay in extracts of punch biopsies from both the lesioned and the contralateral control hemisphere. Hypothermia-induced an overall increase in the concentrations of immunoreactive galanin (p < 0.001). The elevated galanin levels were predominantly found in the non-ischemic control hemisphere, in the hippocampus, thalamus and the posterior part of parietal cortex. The galanin concentrations were lower in the ischemic hemisphere in both the normo- and hypothermic animals compared to the corresponding contra lateral intact hemisphere (p = 0.049). The factor of time, 2 respectively 7 days, did not show any significant difference regarding the galanin concentrations (p = 0.844). Multivariate analyses of variance revealed significant effect of ischemia on the size of the ischemic brain lesions (p = 0.001) but no overall effect of temperature when data from both 2 and 7 days observation periods were analyzed together. The ischemic lesions were generally larger at 33 degrees after 2 days (p = 0.230). Prolonged observation time of 7 days resulted in a significant reduction of the ischemic brain lesion (p = 0.011) with smaller ischemic lesions in the hypothermic group. Our data support the notion that hypothermia-induced increase in the tissue concentrations of galanin in the brain are the result of changes from optimal homeostatic conditions - the hypothermia-induced stress - rather than the ischemia/re-perfusion lesion induced changes in galanin concentrations. Hypothermia-induced elevation in galanin concentration is therefore not likely to be amongst the major protective mechanisms of hypothermia. © 2007 Elsevier Ltd. All rights reserved.
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| 45. |
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| 46. |
- Vukojevic, Vladana, et al.
(author)
-
Fluorescence Imaging with Single-Molecule Sensitivity and Fluorescence Correlation Spectroscopy of Cell-Penetrating Neuropeptides
- 2011
-
In: Neuropeptides. - Totowa, NJ : Humana Press. - 9781617793097 ; 789, s. 147-70
-
Book chapter (peer-reviewed)abstract
- Neuropeptide plasma membrane interactions in the absence of a corresponding specific receptor may result in neuropeptide translocation into the cell. Trans location across the plasma membrane may represent a previously unknown mechanism by which neuropeptides can signal information to the cell interior. We introduce here two complementary optical methods with single-molecule sensitivity, fluorescence imaging with avalanche photodiode detectors (APD imaging) and fluorescence correlation spectroscopy (FCS), and demonstrate how they may be applied for the analysis of neuropeptide ability to penetrate into live cells in real time. APD imaging enables us to visualize fluorescently labeled neuropeptide molecules at very low, physiologically relevant concentrations, whereas FCS enables us to characterize quantitatively their concentration and diffusion properties in different cellular compartments. Application of these methodologies for the analysis of the endogenous opioid peptide dynorphin A (Dyn A), a ligand for the kappa-opioid receptor (KOP), demonstrated that this neuropeptide may translocate across the plasma membrane of living cells and enter the cellular interior without binding to its cognate receptor.
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| 47. |
- Webling, Kristin, et al.
(author)
-
Ala(5)-galanin (2-11) is a GAL2R specific galanin analogue
- 2016
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 60, s. 75-82
-
Journal article (peer-reviewed)abstract
- It is over 30years since the regulatory peptide galanin was discovered by Professor Mutt and co-workers. Galanin exerts its effects by binding to three galanin G-protein coupled receptors, namely GAL1R, GAL2R and GAL3R. Each galanin receptor has a different distribution in the central nervous system and the peripheral nervous system as well as distinctive signaling pathways, which implicates that the receptors are involved in different biological- and pathological effects. The delineation of the galaninergic system is however difficult due to a lack of stable, specific galanin receptor ligands. Herein, a new short GAL2R specific ligand, Ala(5)-galanin (2-11), is presented. The galanin (2-11) modified analogue Ala(5)-galanin (2-11) was tested in (125)I-galanin competitive binding studies for the three galanin receptors and the G-protein coupled receptor signaling properties was tested by the ability to influence second-messenger molecules like inositol phosphate and cyclic adenosine monophosphate. In addition, two different label-free real-time assays, namely EnSpire® based on an optical biosensor and xCELLigence® based on an electric biosensor, were used for evaluating the signaling properties using cell lines with different levels of receptor expression. Ala(5)-galanin (2-11) was subsequently found to be a full agonist for GAL2R with more than 375-fold preference for GAL2R compared to both GAL1R and GAL3R. The single amino acid substitution of serine to alanine at position 5 in the short ligand galanin (2-11) resulted in a ligand subsequently unable to bind neither GAL3R nor GAL1R, even at concentrations as high as 0.1mM.
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| 48. |
- Webling, Kristin, et al.
(author)
-
Pharmacological stimulation of GAL1R but not GAL2R attenuates kainic acid-induced neuronal cell death in the rat hippocampus
- 2016
-
In: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 58, s. 83-92
-
Journal article (peer-reviewed)abstract
- The neuropeptide galanin is widely distributed in the central and peripheral nervous systems and part of a bigger family of bioactive peptides. Galanin exerts its biological activity through three G-protein coupled receptor subtypes, GAL1–3R. Throughout the last 20 years, data has accumulated that galanin can have a neuroprotective effect presumably mediated through the activation of GAL1R and GAL2R. In order to test the pharmaceutical potential of galanin receptor subtype selective ligands to inhibit excitotoxic cell death, the GAL1R selective ligand M617 and the GAL2R selective ligand M1145 were compared to the novel GAL1/2R ligand M1154, in their ability to reduce the excitotoxic effects of intracerebroventricular injected kainate acid in rats.The peptide ligands were evaluated in vitro for their binding preference in a competitive 125I-galanin receptor subtype binding assay, and G-protein signaling was evaluated using both classical signaling and a label-free real-time technique. Even though there was no significant difference in the time course or severity of the kainic acid induced epileptic behavior in vivo, administration of either M617 or M1154 before kainic acid administration significantly attenuated the neuronal cell death in the hippocampus. Our results indicate the potential therapeutic value of agonists selective for GAL1R in the prevention of neuronal cell death.
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| 49. |
- Woldbye, DPD, et al.
(author)
-
Neuropeptide Y and seizures: effects of exogenously applied ligands
- 2004
-
In: Neuropeptides. - : Elsevier BV. - 1532-2785 .- 0143-4179. ; 38:4, s. 253-260
-
Research review (peer-reviewed)abstract
- The endogenous NPY system in the brain is centrally involved in seizure regulation. The present paper reviews the evidence that exogenously applied NPY receptor ligands can inhibit epileptic seizures in various rodent in vitro and in vivo models. Agonists at Y2 and/or Y5 receptors and antagonists at Y1 receptors appear to inhibit seizures, depending on the seizure model studied. Although progress has been made, further studies are needed using transgenic animals as well as novel selective agonists and antagonists to firmly identify the NPY receptors mediating antiepileptic effects. This may lead to the development of future antiepileptic drug treatments targeting the NPY system, (C) 2004 Elsevier Ltd. All rights reserved.
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| 50. |
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