| 1. |
- Blackshear, Alice, et al.
(författare)
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Intracerebroventricular administration of galanin or galanin receptor subtype 1 agonist M617 induces c-Fos activation in central amygdala and dorsomedial hypothalamus
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 28:5, s. 1120-1124
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide galanin and galanin receptors are widespread throughout cortical, limbic and midbrain areas implicated in reward, learning/memory, pain, drinking and feeding. While many studies have shown that galanin produces a variety of presynaptic and postsynaptic responses, work studying the effects of galanin on neural activation is limited. The present study examined patterns of c-Fos immunoreactivity resulting from intracerebro-ventricular administration of galanin versus saline injection in awake rats. An initial comprehensive qualitative survey was conducted to identify regions of high c-Fos expression followed up with quantitative analysis. Galanin induced a significant increase in c-Fos levels relative to saline-treated controls in dorsomedial hypothalamus and in the central nucleus of the amygdala. This pattern of activation was also produced by galanin receptor type 1 agonist M617. The present findings confirm that galanin upregulates c-Fos activation in hypothalamic nuclei, and supports roles for galanin in central amygdala-mediated food intake, and Pavlovian conditioning.
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| 2. |
- Botros, Milad, et al.
(författare)
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Endomorphins interact with the substance P (SP) aminoterminal SP (1-7) binding in the ventral tegmental area of the rat brain
- 2008
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 29:10, s. 1820-1824
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Tidskriftsartikel (refereegranskat)abstract
- We have recently identified a specific binding site for the tachykinin peptide substance P (SP) fragment SP1-7 in the rat spinal cord. This site appeared very specific for SP1-7 as the binding affinity of this compound highly exceeded those of other SP fragments. We also observed that endomorphin-2 (EM-2) exhibited high potency in displacing SP1-7 from this site. In the present work using a [H-3]-labeled derivative of the heptapeptide we have identified and characterized [H-3]-SP1-7 binding in the rat ventral tegmental area (VTA). Similarly to the [H-3]-SP1-7 binding in the spinal cord the affinity of unlabeled SP1-7 to the specific site in VTA was significantly higher than those of other SP fragments. Further, the tachykinin receptor NK-1, NK-2 and NK-3 ligands showed no or negligible binding to the identified site. However, the mu-opioid peptide (MOP) receptor agonists DAMGO, EM-1 and EM-2 did, and significant difference was observed in the binding affinity between the two endomorphins. As recorded from displacement curves the affinity of EM-2 for the SP1-7 site was 4-5 times weaker than that for SP1-7 but about 5 times higher than that of EM-1. The opioid receptor antagonists naloxone and naloxonazine showed weak or negligible binding. it was concluded that the specific site identified for SP1-7 binding in the rat VTA is distinct from the MOP receptor although it exhibits high affinity for EM-2.
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| 3. |
- Carlini, Valeria P., et al.
(författare)
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Melanin-concentrating hormone (MCH) reverts the behavioral effects induced by inescapable stress
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:9, s. 2300-2306
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate if MCH modifies the feeding and freezing responses in rats exposed to stressful stimuli. We used a basic version of contextual fear, where one group of rats were placed in a novel environment and two different groups were exposed to footshock paradigms, one of them escapable and the other one inescapable. At the end of each treatment, freezing and feeding were measured. Only the animals exposed to inescapable footshock paradigm showed significant increase in the food intake and freezing behavior in comparison to the control animals. The MCH administration (intra-hippocampal or intra-amygdaline) reverted these effects elicited by inescapable footshock. Results presented in this paper lead us to the assumption that the anxiolytic effect of the peptide is responsible for the reversion of the IS effects.
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| 4. |
- Ekblad, Eva
(författare)
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CART in the enteric nervous system.
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 27:8, s. 2024-2030
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Forskningsöversikt (refereegranskat)abstract
- The expression, distribution, origin, projections, chemical coding and functions of cocaine and amphetamine-regulated transcript (CART) in the gastro-intestinal tract are reviewed. CART is extensively expressed in the enteric nervous system. Except from being a possible modulator of NO induced intestinal relaxation CART does not seem to play any pivotal role in intestinal motility. Accumulating evidence suggest CART to be neuroprotective, involved in survival and maintenance of enteric neurons. CART expression increases in atrophic intestine thus suggesting a role of CART in intestinal adaptation. In rat antral mucosa CART is expressed in gastrin cells indicating a hormonal role of gastric CART.
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| 5. |
- Gonzalez, Patricia Verónica, et al.
(författare)
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Interleukin-1 beta-induced anorexia is reversed by ghrelin
- 2006
-
Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:12, s. 3220-3225
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Tidskriftsartikel (refereegranskat)abstract
- Interleukins, in particular interleukin-1β (IL-1β), reduce food intake after peripheral and central administration, which suggests that they contribute to anorexia during various infectious, neoplastic, and autoimmune diseases. On the other hand, ghrelin stimulates food intake by acting on the central nervous system (CNS) and is considered an important regulator of food intake in both rodents and humans. In the present study, we investigated if ghrelin could reverse IL-1β-induced anorexia. Intracerebroventricular (i.c.v.) injection of 15, 30 or 45 ng/μl of IL-1β caused significant suppression of food intake in 20 h fasting animals. This effect lasted for a 24 h period. Ghrelin (0.15 nmol or 1.5 nmol/μl) produced a significant increase in cumulative food intake in normally fed animals. However, it did not alter food intake in 20 h fasting animals. Central administration of ghrelin reduced the anorexic effect of IL-1β (15 ng/μl). The effect was observed 30 min after injection and lasted for the next 24 h. This study provides evidence that ghrelin is an orexigenic peptide capable of antagonizing IL-1β-induced anorexia.
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| 6. |
- Haitina, Tatjana, et al.
(författare)
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Further evidence for ancient role of ACTH peptides at melanocortin (MC) receptors; pharmacology of dogfish and lamprey peptides at dogfish MC receptors
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 28:4, s. 798-805
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Tidskriftsartikel (refereegranskat)abstract
- The cloning of melanocortin (MC) receptors in distant species has provided us tools to get insight in how the ligand–receptors interactions in the MC system have evolved. We have however lacked studies on pharmacology of native ancient melanocortin peptides at the ancient MC receptors. In this paper we synthesized melanocortin peptides from both the sea lamprey (Petromyzon marinus) and spiny dogfish (Squalus acanthias) and tested them on the MC3 and MC4 receptors from spiny dogfish. The results show that both the dogfish and lamprey ACTH peptides have similar or higher affinity than the dogfish α-, β- and γ-MSH peptides to the dogfish MC3 and MC4 receptors. Moreover, both the dogfish and lamprey ACTH peptides have more than 10-fold higher affinity than α-MSH to the dogfish MC4 receptor. We also show that dogfish δ-MSH is able to bind to MC receptors and its potency is higher than of dogfish β-MSH, which is considered to be its precursor. Our results provide the first evidence that native ACTH ligands from dogfish and lamprey have a preference above native MSH peptides to ancient version of the MC3 and MC4 receptors. This further strengthens the hypotheses that the ligand contributing to the first version of the melanocortin ligand-receptor system resembled ACTH.
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| 7. |
- Hallberg, Mathias, et al.
(författare)
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The impact of chronic nandrolone decanoate administration on the expression of the NK1 receptor density in rat brain as determined by autoradiography
- 2005
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 26:7, s. 1228-1234
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Tidskriftsartikel (refereegranskat)abstract
- Adult male Sprague–Dawley rats were treated with the anabolic androgenic steroid nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) during 14 days. The effect on the densities of the neurokinin NK1 receptor in brain was examined with autoradiography. An overall tendency of attenuation of NK1 receptor density was observed after completed treatment with nandrolone decanoate. The density of the NK1 receptor was found to be significantly lower compared to control animals in the nucleus accumbens core (37% density reduction), in dentate gyrus (26%), in basolateral amygdaloid nucleus (23%), in ventromedial hypothalamic nucleus (36%), in dorsomedial hypothalamic nucleus (43%) and finally in the periaqueductal gray (PAG) (24%). In the cortex region, no structures exhibited any significant reduction of NK1 receptor density. This result provides additional support to the hypothesis that substance P and the NK1 receptor may be involved as important components that participate in mediating physiological responses including the adverse behaviors often associated with chronically administrated anabolic androgenic steroids in human.
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| 8. |
- Jackson, Graham E, et al.
(författare)
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Solution conformations of an insect neuropeptide : crustacean cardioactive peptide (CCAP)
- 2009
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:3, s. 557-564
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Tidskriftsartikel (refereegranskat)abstract
- The solution structure of crustacean cardioactive peptide (CCAP), a cyclic amidated nonapeptide neurohormone, was studied using molecular dynamics techniques, with constraints derived from NMR studies in water and water/dodecylphosphocholine micellar medium. This peptide, found in various invertebrates, has the primary sequence Pro(1) Phe(2) Cys(3) Asn(4) Ala(5) Phe(6) Thr(7) Gly(8) Cys(9) NH(2), with an intramolecular disulfide bridge between the two cysteine residues. In aqueous solution the peptide was found to have a type(IV) beta-turn between residues 5-8. In a water/decane biphasic medium a type(IV) beta-turn between residues 3 and 6 and two classic gamma-turns between residues 4-6 and 7-9, were found. Analysis of the (1)H and (13)C NMR chemical shifts data showed that the model free S(2) order parameter of the residues varied between 0.65 and 0.9. The molecular dynamic root mean square fluctuations of structural ensembles of the backbone varied between 0.5 and 2.2 with the central residues showing the least fluctuations.
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| 9. |
- Johansson, Andreas, et al.
(författare)
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The relative impact of chronic food restriction and acute food deprivation on plasma hormone levels and hypothalamic neuropeptide expression
- 2008
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 29:9, s. 1588-1595
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the central regulation of food intake and body weight has increased tremendously through implication of a high number of neuropeptides. However, lack of all-embracing studies have made comparison difficult in the past. The objective of this study was to demonstrate the relative importance of the different neuropeptides in terms of involvement in appetite regulatory mechanisms. We quantified expression levels of 21 hypothalamic neuropeptides and circulating levels of leptin, insulin, corticosterone, adrenocorticotropic hormone, ghrelin and adiponectin in rats after acute food deprivation and chronic food restriction using validated quantitative real-time PCR and hormone measurements. Body weight, insulin and leptin were reduced whereas corticosterone was increased by both acute food deprivation and chronic food restriction. Our results confirmed the relative importance in body weight homeostasis of neuropeptide Y and proopiomelanocortin, which were increased and decreased as predicted. The expression of other neuropeptides previously attributed central roles in body weight homeostasis, e.g. melanin-concentrating hormone and orexin, appeared to be less affected by the treatments. Moreover, the expression of dynorphin, galanin-like peptide and neuropeptide B was dramatically reduced after both treatments. This suggests that the latter neuropeptides--although previously known to be involved in body weight homeostasis--may be of unexpected importance in states of negative energy balance.
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| 10. |
- Jönsson, Maria, 1980-, et al.
(författare)
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Substance P and the neurokinin-1 receptor in relation to eosinophilia in ulcerative colitis
- 2005
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 26:5, s. 799-814
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Tidskriftsartikel (refereegranskat)abstract
- Substance P (SP) has been implicated in the pathophysiology of ulcerative colitis (UC) and it has been suggested that blocking of its effect would be advantageous in this disease. Eosinophils have also been implicated in the pathophysiology of UC. In the present study, specimens from the sigmoid colon of UC patients were investigated by the use of antisera against SP and the neurokinin-1 receptor (NK-1R) and staining for demonstration of eosinophils. The degrees of SP innervation and NK-1R immunoreaction, as well as the levels of eosinophil infiltration, varied between different patients. Interestingly, NK-1R immunoreaction in the epithelium was often seen to be the most marked where there were numerous eosinophils in the underlying mucosa and where the mucosa showed a marked morphologic derangement. The observations suggest that there are marked fluctuations in effects of SP and eosinophils during the disease. The infiltrating eosinophils may be involved in the destruction of the mucosal tissue. Furthermore, for the majority of cases where there is marked derangement of the mucosa, it is apparent that there is an upregulation of the NK-1 receptor in the epithelium in parallel with the infiltration of the eosinophils.
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| 11. |
- Larsson, Tomas A, et al.
(författare)
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Characterization of NPY receptor subtypes Y2 and Y7 in rainbow trout Oncorhynchus mykiss
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:6, s. 1320-1327
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Tidskriftsartikel (refereegranskat)abstract
- We report the cloning and pharmacological characterization of two neuropeptide Y (NPY) receptor subtypes, Y2 and Y7, in rainbow trout (Oncorhynchus mykiss). These subtypes are approximately 50% identical to each other and belong to the Y2 subfamily of NPY receptors. The binding properties of the receptors were investigated after expression in human HEK-293 EBNA cells. Both receptors bound the three zebrafish peptides NPY, PYYa, and PYYb, as well as porcine NPY and PYY, with affinities in the nanomolar range that are similar to mammalian Y2. The affinity of the truncated porcine NPY fragments, NPY 13-36 and NPY 18-36 was markedly lower compared to mammalian and chicken Y2. This suggests that mammalian and chicken Y2 are unique among NPY receptors in their ability to bind truncated peptide fragments. The antagonist BIIE0246, developed for mammalian Y2, did not bind either of the two rainbow trout receptors. Our results support the proposed expansion of this gene family by duplications before the gnathostome radiation. They also reveal appreciable differences in the repertoire and characteristics of NPY receptors between fish and tetrapods stressing the importance of lineage-specific gene loss as well as sequence divergence after duplication.
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| 12. |
- Magnusson, Kristina, et al.
(författare)
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Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 28:4, s. 851-858
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Tidskriftsartikel (refereegranskat)abstract
- The misuse of anabolic androgenic steroids (AAS) seems to produce profound effects on the central nervous system, leading to aggressive behavior and increased sensitivity to other drugs of abuse. The present study addresses the effect on the enzymatic transformation, here called dynorphin converting enzyme-like activity. The formation of the mu/delta opioid peptide receptor-preferring Leu-enkephalin-Arg6 from the kappa opioid peptide receptor-preferring dynorphin A was measured in rats treated with nandrolone decanoate. Significant variations in enzymatic transformation were observed in several brain regions. An altered receptor activation profile in these regions may be one contributory factor behind AAS-induced personality changes.
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| 13. |
- Muceniece, Ruta, et al.
(författare)
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The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:6, s. 1443-1450
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Tidskriftsartikel (refereegranskat)abstract
- Melanocortins possess strong anti-inflammatory effects acting in the central nervous system via inhibition of the production of nitric oxide (NO) during brain inflammation. To shed more light into the role of melanocortin (MC) receptor subtypes involved we synthesized and evaluated some novel peptides, modified in the melanocyte-stimulating hormone (MSH) core structure, natural MCs and known MC receptor selective peptides - MS05, MS06. Since the study included both selective, high affinity binders and the novel peptides, it was possible to do the correlation analysis of binding activities and the NO induction-related anti-inflammatory effect of the peptides. beta-MSH, gamma1-MSH, gamma2-MSH, alpha-MSH, MS05, Ac-MS06 and Ac-[Ser12]MS06 caused dose dependent inhibition of the lipopolysaccharide (LPS)-induced increase of NO overproduction in the mice forebrain whereas MSH core modified peptides Ac-[Asp9,Ser12]MS06, [Asp9]alpha-MSH and [Asp16]beta-MSH were devoid of this effect in doses up to 10 nmol per mouse. When the minimal effective dose required for inhibition of NO production was correlated with the in vitro binding activity to MC receptor subtypes a strong and significant correlation was found for the MC3 receptor (r = 0.90; p = 0.0008), whereas weak correlation was present for the other receptors. Our results suggest that the MC3 receptor is the major player in mediating the anti-inflammatory activity of MCs in the central nervous system.
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| 14. |
- Mutulis, Felikss, et al.
(författare)
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N-alkylated dipeptide amides and related structures as imitations of the melanocortins' active core
- 2005
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 26:10, s. 1997-2016
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-three low molecular mass structures combining both peptide and peptoid features were prepared and tested on human melanocortin receptors MC1,3-5R. Most of them displayed low micromolar activity with preference for diamines, guanidino and 2-naphthyl derivatives compared to monoacetylated, amino and 3-indolyl counterparts. Some contained L- or D-histidine residues, but the change did not influence affinity. QSAR modelling yielded excellent models for the MC3-5 receptors explaining R2Y=0.89-0.91 and predicting Q2=0.77-0.80 of the affinity variations. One compound displayed MC1R selectivity (13-fold and more). An NMR study of showed that it exists as a mixture of four rotamers at its tertiary amide bonds. Comparisons with earlier data for melanocortin core tetrapeptide analogues indicate that the novel peptide-peptoids interact with the melanocortin receptors in a different way.
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| 15. |
- Olinski, Robert, et al.
(författare)
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Three insulin-relaxin-like genes in Ciona intestinalis
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:11, s. 2535-2546
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Tidskriftsartikel (refereegranskat)abstract
- The Ciona intestinalis genome harbors three insulin-like genes: INS-L1, -L2 and -L3. Conserved synteny between the Ciona-human genomes predicts that Ciona INS-Ls are orthologous to the vertebrate insulin-relaxin family, but this relation cannot be inferred from molecular phylogeny. A conserved protein core with six cysteines; typical arrangement of B-, C- and A-protein domains; pro-protein maturation mode; and putative insulin receptor-binding sites were identified in Ciona INS-L proteins. ESTs used to assemble exonic sequences of INS-Ls combined with qRT-PCR analysis provided evidence that the predicted genes are expressed in the developing and adult Ciona. Our results support that Ciona INS-L1 is orthologous to the vertebrate insulin-like/relaxin genes, INS-L2 to insulin genies and INS-L3 to IGF genes. Our analysis also implies that the insulin-like/relaxin ancestor switched receptor type from tyrosine kinase- to GPCR-type, whereas insulin-IGF subfamily retained the tyrosine kinase-type of receptor. We propose that this receptor-switch occurred after the time when urochordates branched from the common chordate lineage, but before the two genome-duplications at the root of the vertebrates. (c) 2006 Elsevier Inc. All rights reserved.
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| 16. |
- Olszewski, Pawel K., et al.
(författare)
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Alpha-melanocyte stimulating hormone and ghrelin : central interaction in feeding control
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 28:10, s. 2084-2089
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-melanocyte stimulating hormone (alpha-MSH) and ghrelin play significant yet opposite roles in the regulation of feeding: alpha-MSH inhibits, whereas ghrelin stimulates consumption. The two peptidergic systems may interact in the process of food intake control. A single report published thus far has shown that a synthetic agonist of the melanocortin receptors, MTII, injected in the hypothalamic paraventricular nucleus (PVN) decreases feeding generated by ghrelin. We found that very low doses of alpha-MSH and MTII administered ICV significantly reduced ghrelin-dependent hyperphagia. However, an endogenous molecule, alpha-MSH, infused in the PVN did not exert an inhibitory effect on ghrelin-induced consumption, whereas the effective dose of PVN MTII exceeded that necessary to decrease short-term deprivation-induced feeding. We conclude that it is likely that in feeding regulation alpha-MSH and ghrelin "interact" at the central nervous system level, but the involvement of the PVN in this interaction appears questionable.
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| 17. |
- Olszewski, Pawel K, et al.
(författare)
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Complexity of neural mechanisms underlying overconsumption of sugar in scheduled feeding : involvement of opioids, orexin, oxytocin and NPY
- 2009
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:2, s. 226-233
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Tidskriftsartikel (refereegranskat)abstract
- A regular daily meal regimen, as opposed to ad libitum consumption, enforces eating at a predefined time and within a short timeframe. Hence, it is important to study food intake regulation in animal feeding models that somewhat reflect this pattern. We investigated the effect of scheduled feeding on the intake of a palatable, high-sugar diet in rats and attempted to define central mechanisms - especially those related to opioid signaling--responsible for overeating sweet foods under such conditions. We found that scheduled access to food, even as challenging as 20 min per day, does not prevent overconsumption of a high-sucrose diet compared to a standard one. An opioid receptor antagonist, naloxone, at 0.3-1 mg/kg b. wt., decreased the intake of the sweet diet, whereas higher doses were required to reduce bland food consumption. Real-time PCR analysis revealed that expression of hypothalamic and brainstem genes encoding opioid peptides and receptors did not differ in sucrose versus regular diet-fed rats, which suggests that scheduled intake of sweet food produces only a transient change in the opioid tone. Intake of sugar was also associated with upregulation of orexin and oxytocin genes in the hypothalamus and NPY in the brainstem. We conclude that scheduled consumption of sugar diets is associated with activity of a complex network of neuroregulators involving opioids, orexin, oxytocin and NPY.
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| 18. |
- Palm, Caroline, et al.
(författare)
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Quantitatively determined uptake of cell-penetrating peptides in non-mammalian cells with an evaluation of degradation and antimicrobial effects
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:7, s. 1710-1716
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Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) are carriers developed to improve mammalian cell uptake of important research tools such as antisense oligonucleotides and short interfering RNAs. However, the data on CPP uptake into non-mammalian cells are limited. We have studied the uptake and antimicrobial effects of the three representative peptides penetratin (derived from a non-mammalian protein), MAP (artificial peptide) and pVEC (derived from a mammalian protein) using fluorescence HPLC in four common model systems: insect cells (Sfg), gram-positive bacteria (Bacillus megaterium), gram-negative bacteria (Escherichia coli) and yeast (Saccharomyces cerevisiae). We demonstrate that non-mammalian cells internalize CPPs and a comparison of the uptake of the peptides show that the intracellular concentration and degradation of the peptides varies widely among organisms. In addition, these CPPs showed antimicrobial activity.
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| 19. |
- Pickering, Chris, et al.
(författare)
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The role of hypothalamic peptide gene expression in alcohol self-administration behavior.
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 28:12, s. 2361-2371
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Tidskriftsartikel (refereegranskat)abstract
- Self-administration of ethanol and food share many common features and Richter hypothesized that an increase in ethanol consumption would decrease feeding to balance the excess calories contained in the ethanol. Previously, we have shown that individual alcohol consumption correlates with neurotransmitter gene expression, especially in the prefrontal cortex. To test the hypothesis of Richter, we measured hypothalamic gene expression of receptors or neuropeptides of known relevance for the regulation of food intake using qPCR and correlated this to individual ethanol consumption in Wistar rats. For validation, gene expression was first correlated with body weight. We found a correlation of dynorphin, somatostatin, melanocortin-4 receptor and serotonin 5-HT2C with body weight and trends to correlation for CART, thus confirming the established role of the hypothalamus in the regulation of weight. For ethanol consumption, correlations were found for CRH receptors I and 2 and vasopressin while strong trends were observed for galanin receptor 1, orexin receptor 1, MCH and adrenoceptor alpha(1B). Therefore, alcohol consumption does seem to involve several hypothalamic systems which also mediate feeding responses and suggests that the hypothalamus, together with the prefrontal cortex, may determine the 'stopping point' of an individual.
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| 20. |
- Poels, Jeroen, et al.
(författare)
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Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6.
- 2009
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:3, s. 545-56
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptides related to vertebrate tachykinins have been identified in Drosophila and are referred to as drosotachykinins, or DTKs. Two Drosophila G protein-coupled receptors, designated NKD (neurokinin receptor from Drosophila; CG6515) and DTKR (Drosophila tachykinin receptor; CG7887), display sequence similarities to mammalian tachykinin receptors. Whereas DTKR was shown to be activated by DTKs [Birse RT, Johnson EC, Taghert PH, Nässel DR. Widely distributed Drosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides. J Neurobiol 2006;66:33-46; Poels J, Verlinden H, Fichna J, Van Loy T, Franssens V, Studzian K, et al. Functional comparison of two evolutionary conserved insect neurokinin-like receptors. Peptides 2007;28:103-8] and was localized by immunocytochemistry in Drosophila central nervous system (CNS), agonist-dependent activation and distribution of NKD have not yet been investigated in depth. In the present study, we have challenged NKD-expressing mammalian and insect cells with a library of Drosophila neuropeptides and discovered DTK-6 as a specific agonist that can induce a calcium response in these cells. In addition, we have produced antisera to sequences from NKD protein to analyze receptor distribution. We found that NKD is less abundantly distributed in the central nervous system than DTKR, and only NKD was found in the intestine. In fact, the two receptors are distributed in mutually exclusive patterns in the CNS. The combined distribution of the receptors in brain neuropils corresponds well with the distribution of DTKs. Most interestingly, NKD appears to be activated only by DTK-6, known to possess an Ala-substitution in an otherwise conserved C-terminal core motif. Our findings suggest that NKD and DTKR provide substrates for two functionally and spatially separated peptide signaling systems.
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| 21. |
- Schiöth, Helgi B, et al.
(författare)
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Evolutionary conservation of the structural, pharmacological, and genomic characteristics of the melanocortin receptor subtypes
- 2005
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 26:10, s. 1886-1900
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Tidskriftsartikel (refereegranskat)abstract
- We have cloned melanocortin receptors (MCRs) from several species of fish. The MC4R and MC5R subtypes arose early in vertebrate evolution and their primary structure is remarkably conserved. Expression and pharmacological characterization of the MCRs in fish has revealed that they bind and respond to melanocortin peptides with high potency. Detailed characterization of the binding properties of the different subtypes suggests that MCRs in early vertebrates had preference for adrenocorticotropic hormone (ACTH) peptides, while the high sensitivity for the shorter proopiomelanocortin (POMC) products, such as the α-, β-, and γ-melanocyte-stimulating hormone (MSH), has appeared later, perhaps as the MCR subtypes gained more specialized functions. The MCR repertoire shows in general high similarities in their primary structures, while they are however not similar in terms of functional roles. The MCRs serve therefore as an interesting model family to understand the molecular mechanisms of how functions of the genes can diverge during evolution. In this review, we provide an overview of our recent studies on the cloning, expression, pharmacology, 3D modeling, and genomic studies of the MCRs in non-mammalian species.
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| 22. |
- Sjögren, M., et al.
(författare)
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Antifouling activity of synthesized peptide analogs of the sponge metabolite barettin
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:9, s. 2058-2064
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Tidskriftsartikel (refereegranskat)abstract
- Barettin (cyclo [(6-bromo-8-en-tryptophan) arginine]), a diketopiperazine isolated from the marine sponge Geodia barretti, is a potent inhibitor of barnacle larvae settlement with an EC50-value of 0.9 mu M. In the present study, 14 analogs of barettin and its structural congener dipodazine were synthezised and tested for their ability to inhibit larval settlement. Two of the analogs have an intact barettin skeleton. The remaining analogs have a dipodazine skeleton (a diketopiperazine where arginine is replaced with glycine). Six of the tested synthetic analogs displayed significant settlement inhibition with the most potent inhibitor being benzo[g]dipodazine, which displayed even stronger activity than barettin (EC50-value 0.034 mu M). The effect of benzo[g]dipodazine was also shown to be readily reversible, when cyprids were transferred to filtered seawater (FSW). (c) 2006 Elsevier Inc. All rights reserved.
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| 23. |
- Sörhede Winzell, Maria, et al.
(författare)
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Role of VIP and PACAP in islet function
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 28:9, s. 1805-1813
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Tidskriftsartikel (refereegranskat)abstract
- Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two closely related neuropeptides that are expressed in islets and in islet parasympathetic nerves. Both peptides bind to their common G-protein-coupled receptors, VPAC1 and VPAC2, and PACAP, in addition to the specific receptor PAC1, all three of which are expressed in islets. VIP and PACAP stimulate insulin secretion in a glucose-dependent manner and they both also stimulate glucagon secretion. This action is achieved through increased formation of cAMP after activation of adenylate cyclase and stimulation of extracellular calcium uptake. Deletion of PAC1 receptors or VPAC2 receptors results in glucose intolerance. These peptides may be of importance in mediating prandial insulin secretion and the glucagon response to hypoglycemia. Animal studies have also suggested that activation of the receptors, in particular VPAC2 receptors, may be used as a therapeutic approach for the treatment of type 2 diabetes. This review summarizes the current knowledge of the potential role of VIP and PACAP in islet function.
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| 24. |
- Thorsell, Annika
(författare)
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Neuropeptide Y (NPY) in alcohol intake and dependence
- 2007
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 28:2, s. 480-483
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y has a role in alcohol intake and dependence. NPY's effect on alcohol intake appears to be in part dependent on the individual's history of alcohol dependence. In models of high intake such as alcohol-preferring, selectively bred rat lines (e.g., the P-line and the HAD line), as well as in ethanol-vapor-exposed subjects, NPY modulates alcohol intake while leaving it unaffected during baseline conditions. The primary receptor subtype mediating NPY's effect on ethanol intake remains in question. The Y2-antagonist BIIE0246 significantly suppresses ethanol intake in an operant paradigm with a sensitization to the effect of BIIE0246 in vapor-exposed subjects. We propose the NPY system to be one of the most interesting target systems for the development of treatments for alcohol abuse and dependence.
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| 26. |
- Zhou, Qin, et al.
(författare)
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The C-terminal amidated analogue of the Substance P (SP) fragment SP (1-7) attenuates the expression of naloxone- precipitated withdrawal in morphine dependent rats
- 2009
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:12, s. 2418-2422
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Tidskriftsartikel (refereegranskat)abstract
- We previously demonstrated that intracerebroventricular (i.c.v.) administration of the substance P (SP) aminoterminal fragment SP(1-7) attenuates the expression of morphine withdrawal in the male rat. In this study we have used a synthetic analogue of this peptide, i.e. the SP(1-7) amide showing higher binding potency than the native heptapeptide, in a similar experimental set-up. Thus, Wistar male rats were made tolerant to morphine by daily injections of the opiate during 8 days. Following peptide administration (i.c.v.) and a subsequent naloxone challenge a variety of physical syndromes of withdrawal were recorded. We observed that the SP(1-7) amide potently and dose-dependently reduced several signs of reaction to morphine withdrawal. Interestingly, the effect of the peptide amide was significantly attenuated by the addition of the sigma agonist (+)-SKF-10047. We conclude that the SP(1-7) amide mimics the effect of the native SP fragment and that the mechanisms for its action involve a sigma receptor site.
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| 27. |
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| 37. |
- Theodorsson, Annette, et al.
(författare)
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Estradiol increases brain lesions in the cortex and lateral striatum after transient occlusion of the middle cerebral artery in rats: No effect of ischemia on galanin in the stroke area but decreased levels in the hippocampus
- 2005
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 26:11, s. 2257-2264
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Tidskriftsartikel (refereegranskat)abstract
- A distinctive feature of galanin expression is that it is extensively increased by neuronal injury, estrogens, Alzheimer's disease and during development. Since stroke is amongst the clinically most important causes of neuronal injury we studied the tissue concentrations of galanin in a rat stroke model and the possibility of modulating this effect with estrogen. Transient focal middle cerebral artery ischemia was induced in rats that 2 weeks earlier underwent ovariectomy and received 1.5 mg 17β-estradiol slow-release or placebo pellets. The concentrations of galanin and neuropeptide Y were measured after observation periods of 3, 7 and 14 days in extracts of punch biopsies from both the lesioned and the contra lateral control hemisphere. The galanin levels were not changed in any of the brain regions studied except in the hippocampus where they were lower in the ischemic hemisphere in both the estrogen- and placebo-treated animals compared to the corresponding contra lateral intact hemisphere (p = 0.015). Estrogen treatment up-regulated galanin concentrations in both the ventral and dorsal hippocampus (p = 0.003). The effects on the galanin concentrations were similar after all observation periods: 3, 7 and 14 days (p = 0.144). No significant changes were observed in the concentration of neuropeptide Y in response to the lesions. The ischemic lesions were markedly larger in the estrogen-treated animals observed after 3 days compared to the corresponding control group. In the estrogen group the lesion was largest at bregma and the slice 2 mm anterior to the bregma, 82% and 435% larger than in the control group (p < 0.001). A similar, but much less pronounced (not statistically significant) difference was seen in the groups observed after 7 and 14 days. Earlier studies of lesions in the peripheral and central nervous systems have generally shown an up-regulation of galanin markers in response to but at a distance from the injury. Our results indicate that galanin is not involved in the response of the ischemic penumbra itself to stroke, whereas it may participate in the reactions of the neural stem-cell rich hippocampus to stroke.
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