| 1. |
- Nilsson, Isabelle, 1971-, et al.
(författare)
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Pharmacological analysis of CCK2 receptor ligands using COS-7 and SK-N-MC cells, expressing the human CCK2 receptor
- 2002
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Ingår i: Regulatory Peptides. - 1873-1686 .- 0167-0115. ; 103:1, s. 29-37
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Tidskriftsartikel (refereegranskat)abstract
- A series of CCK2 receptor ligands were analysed with respect to their interaction with binding sites in the membranes of COS-7 cells and SK-N-MC cells transiently expressing the human CCK2 receptor (short isoform). The ligands were YF476, YM022, AG041R, L-740,093, JB93182, PD134308, and PD136450. Their binding was analysed by radioligand competition using [H-3]L-365,260 as the labelled ligand. Saturation binding analysis indicated that [H-3]L-365,260 interacted with a single class of binding sites. In competition binding experiments using COS-7-cell membranes, all seven ligands were incubated together with 2 nM [H-3]L-365,260. The data for four of the compounds fitted a one-site model (pK(i) values: YM022: 9.2 +/- 0.02, YF476: 9.6 +/- 0.04; L-740,093: 9.2 +/- 0.01, and AG041R: 8.3 +/- 0.06), while the data for the three others fitted a two-site model (pK(i) values: JB93182: 8.8 +/- 0.04 and 6.0 +/- 0.15; PD 134308: 9.0 +/- 0.04 and 6.1 +/- 0.15; and PD 136450: 9.0 +/- 0.02 and 5.4 +/- 0.41). SK-N-MC cell membranes and 2 nM [H-3]L-365,260 were incubated together with YM022, YF476, JB93182, and PD134308. The data for YM022 and YF476 fitted a one-site model (pKi values: YM022: 9.3 +/- 0.06, YF476: 9.4 +/- 0.02), while the data for JB93182 and PD134308 fitted a two-site model (pK(i) values: JB93182: 8.7 +/- 0.06 and 6.2 +/- 0.06; PD134308: 9.1 +/- 0.06 and 7.0 +/- 0.17). Competition binding experiments in the presence of the GTP-analogue guanylylimidodiphosphate, using either of the two cell types, produced similar binding data for PD 134308 and JB93182 as in the absence of GTP-analogue. The human receptor seems to exist in a low and/or high affinity state. The shift from low to high affinity does not seem to reflect the degree of G protein coupling.
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| 2. |
- Portela-Gomes, GM, et al.
(författare)
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PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas - Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets
- 2003
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Ingår i: Regulatory Peptides. - 1873-1686 .- 0167-0115. ; 113, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet neuropeptide with potent insulinotropic action. The current study investigates PACAP expression in normal human and rat pancreatic islets, and whether it is altered in diabetic state. To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique. Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat. PACAP immunoreactivity was observed in virtually all insulin and glucagon cells in both species, but not in somatostatin or pancreatic polypeptide (PP) cells; this co-localization pattern was unaltered in diabetic pancreata. In normal human pancreas, PACAP was further localized ultrastructurally to the secretory granules of insulin and glucagon cells. PACAP significantly potentiated glucose-stimulated insulin release in isolated islets of normal but not of GK rats. PACAP failed to enhance cAMP generation in normal islets, but induced similar to 5-folds exaggeration in the diabetic islets. In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells. Furthermore, the insulinotropic action of PACAP was markedly impaired in diabetic islets in spite of exaggerated cAMP response. (C) 2003 Elsevier Science B.V. All rights reserved.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- El-Salhy, M, et al.
(författare)
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Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy
- 2000
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 88:1-3, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.
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| 7. |
- El-Salhy, Magdy, et al.
(författare)
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Triple therapy with octreotide, galanin and serotonin induces necrosis and increases apoptosis of a rat colon carcinoma
- 2002
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Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 108:2-3, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- A rat colonic adenocarcinoma was implanted subcutaneously (s.c.) in nude mice. After 7 days, the animals were divided into different groups. Two groups received subcutaneous injections twice daily with 3 or 6 μg/kg body weight octreotide, galanin and serotonin. Three groups were respectively treated with 20, 30, and 40 μg/kg body weight of the previously mentioned bioactive substances. Control group received only saline solution in the same fashion as treated animals. The treatment lasted for 5 days. The tumour volume and weight, the relative density of blood vessels, of tumour necrotic tissue, of apoptotic nuclei and of proliferating nuclei were measured. Apoptosis was detected by in situ labelling of nuclear DNA fragmentation according to TUNEL method, and proliferation by immunocytochemistry. Morphometry was done with the classical stereological point-counting method. Food consumption, animal weight, faeces weight and its water content were measured for 3 days before and after treatment. Triple therapy with 3 and 6 μg/kg body weight had no effect on any of the parameters measured, except in reducing the relative volume density of tumour blood vessels. Treatment with 20, 30 and 40 μg/kg body weight of the previously mentioned bioactive substances reduced the tumour volume, the relative volume density of blood vessels and increased the relative volume density of necrotic tissue and of apoptotic nuclei (in the 20 μg group). However, there was no difference between treated mice and controls regarding the relative volume density of proliferating nuclei. There was no statistical difference between treated animals regarding food consumption, body weight, faeces weight and its water content before and during treatment. The present study confirms that triple therapy with octreotide, galanin and serotonin causes regression of a rat colon carcinoma. It further showed that optimum treatment dose is 20 μg/kg body weight of each bioactive substance. Moreover, this therapy regime does not show apparent side effects in the experiments carried out on mice.
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| 8. |
- El-Salhy, Magdy, et al.
(författare)
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Triple therapy with octreotide, galanin, and serotonin reduces the size and blood vessel density and increases apoptosis of a rat colon carcinoma
- 2003
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Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 111:1-3, s. 145-152
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Tidskriftsartikel (refereegranskat)abstract
- A rat colonic adenocarcinoma was implanted subcutaneously in female nude (C57BL/6JBom-nu) mice. After 7 days, the animals were divided into different groups. One group received triple therapy with octreotide, galanin, and serotonin, 10 μg/kg body weight of each, twice daily. The second group served as controls and received only saline solution. Three groups received 10 μg/kg body weight twice daily of octreotide, galanin, or serotonin. The last group consisted of controls that received only saline solution. The treatment lasted for 5 days. The tumour volume, wet weight, and relative volume density of blood vessels were significantly decreased after the triple treatment, as compared to controls. Apoptotic index was significantly increased, but the proliferation index was not affected in the group of mice that received triple therapy. There was no significant difference between controls and mice treated with octreotide, galanin, or serotonin regarding tumour volume or weight. The relative volume density of blood vessels was decreased in tumours treated with galanin, but not with octreotide or serotonin. There was no statistical difference in the proliferation index between controls and animals treated with octreotide, galanin, or serotonin, as compared with controls. Tumour necrosis and increased apoptosis may be responsible for the reduction in the volume and weight of the tumour after triple therapy. Tumour necrosis may be caused by the induction of tumour ischemia due to a reduction in tumour blood flow, which is caused by decreased incidence of tumour-feeding blood vessels, and by constriction of tumour-feeding arterioles. These results are promising and may offer treatment for colon cancer.
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| 9. |
- Ericson, Ann-Charlott, 1965-, et al.
(författare)
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Morphological examination of the termination pattern of substance P-immunoreactive nerve fibers in human antral mucosa
- 2002
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 107:1-3, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- The termination pattern of substance P (SP)-containing axons in human antral mucosa was examined using immunohistochemical techniques at the light and electron microscopic level. SP-immunoreactive (IR) axons were found to extend towards the pit region of the glands, where intraepithelial axons were observed. Electron microscopy showed immunostained axon profiles in close contact with the basement membrane of surface mucous cells. Membrane-to-membrane contacts between labeled axons and myofibroblast-like cells were identified, and SP-IR axons that were apposed to the epithelium were also in contact with subjacent myofibroblast-like cells. The anatomical relationship between SP-IR axons and the cells of the muscularis mucosae was investigated by light microscopy. Immunoreactivity for a-smooth muscle actin (a-sma) was used to visualize the smooth muscle cells, and the a-sma-IR cells were found to create a network that surrounded the gastric glands. Immunostained varicose axons ran alongside and in close apposition to the labeled muscle strands. Ultrastructural examination showed close contacts between SP-IR axon profiles and smooth muscle-like cells. In conclusion, SP-containing neurons may be important for sensory and secretomotor functions in the human antral mucosa.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Nilsson, Isabelle, 1971-, et al.
(författare)
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Molecular cloning of an unusual bicistronic cholecystokinin receptor mRNA expressed in chicken brain : a structural and functional expression study
- 2003
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 114:1, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- This report describes the molecular cloning and pharmacological characterization of a transiently expressed chicken brain cholecystokinin receptor (CCK-CHR) in COS-7 cells. A polymerase chain reaction (PCR)-based cloning strategy was applied using: (1) an initial PCR with deoxyinosine-containing primers designed to target conserved regions in CCK receptors, followed by (2) rapid amplification of cDNA ends (RACE), and (3) full-length PCR of the CCK-CHR cDNA. The full-length cloned bicistronic CCK-CHR cDNA contained a short upstream open reading frame (uORF) coding for a putative six-amino-acid-long peptide of unknown function, followed by a long open reading frame (lORF) encoding the 436-amino-acid-long CCK-CHR receptor protein. At the amino acid level, the CCK-CHR shared ∼50% homology with mammalian and Xenopus laevis CCK receptors. The pharmacological profile of CCK-CHR resembled that of CCK-B receptors using agonists (CCK-8, CCK-4, gastrin-17), whereas CCK-CHR showed higher affinity for the CCK-A receptor antagonist, devazepide, than for the CCK-B receptor antagonist, l-365,260. To the best of our knowledge, this is the first description and functional expression study of a cloned chicken CCK receptor cDNA.
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| 14. |
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| 15. |
- Rugarn, Olof, et al.
(författare)
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Progesterone and norethisterone have different effects on tachykinin-like immunoreactivity in rat cortex and striatum
- 2001
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 101:1-3, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to investigate the effects of progesterone and the most commonly prescribed synthetic progestogen, norethisterone, on regional immune-like reactivity of neuropeptide Y (NPY), substance P (SP), neurokinin A (NKA) and neurotensin (NT) in brains of female ovariectomized estradiol-substituted rats.Results: Norethisterone+estradiol-treated rats had 44% lower SP levels compared with estradiol-only-treated in frontal cortex and 20% lower NKA levels in comparison with progesterone+estradiol-treated in frontal cortex. Progesterone+estradiol-treated rats had 66% lower SP levels in striatum in comparison with both estradiol-only-treated and norethisterone+estradiol-treated. No significant results were found for NPY and NT.Conclusion: Progesterone and the synthetic progestogen, norethisterone, have different effects on SP- and NKA-like immunoreactivity in rat cortex and striatum.The effects of NET on SP- and NKA-like immunoreactivity in frontal cortex may contribute to the mood effects ascribed to this progestogen in clinical usage.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Trulsson, Lena M., 1950-, et al.
(författare)
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Cholecystokinin octapeptide induces both proliferation and apoptosis in the rat pancreas
- 2001
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 98:1-2, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin-8 (CCK-8) causes exocrine pancreatic hypertrophy and hyperplasia. High doses of the CCK analogue cerulein causes necrosis and an inflammatory response in the pancreas. We have studied the pancreatic growth response in rats after administration of CCK-8 for 3 days, given either intermittently (20–80 μg/kg) twice a day, or continuously (2.4–48 μg/kg per 24 h). Plasma CCK-8 levels, pancreatic wet weight, water, protein and DNA contents and the pancreatic caspase-3 activity were measured. Cell proliferation was visualized by [3H]thymidine incorporation and apoptosis by TUNEL reaction. Continuous administration of CCK-8 dose-dependently increased the plasma CCK levels, the pancreatic wet weight, protein and DNA contents as well as thymidine labeling index, apoptotic index and caspase-3 activity. Intermittent injections of CCK-8 caused transient raises in plasma CCK, increased apoptotic index and caspase-3 activity, a dose-dependent increase in thymidine labeling but caused a dose-dependent reduction of pancreatic wet weight, protein, and DNA contents. It is concluded that CCK-8 causes both increased proliferation and apoptosis in the pancreas. In case of continuous administration of CCK-8, the proliferation outweighs the apoptosis causing hyperplasia but in the case of intermittent administration the opposite effect is seen.
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| 22. |
- Trulsson, Lena, 1950-, et al.
(författare)
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The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas
- 2002
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 106:1-3, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by Nω-nitro-l-arginine (l-NNA) reduced the urinary excretion of NO2/NO3 and raised serum l-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO2/NO3. The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, l-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of l-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Ehrström, M, et al.
(författare)
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Pharmacokinetic profile of orexin A and effects on plasma insulin and glucagon in the rat
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 119:3, s. 209-212
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Tidskriftsartikel (refereegranskat)abstract
- Orexin A (OXA) is found in the central nervous system (CNS) and in the gut. Peripheral administration of OXA to rats results in an inhibition of fasting motility. Plasma OXA increases during fasting and central administration of OXA increases food intake. The aim of the present study was to assess the pharmacokinetic profile of OXA and the effect of intravenously (IV) administered OXA on plasma concentrations of insulin and glucagon concentrations. Rats were given OXA IV (100 pmol kg-1 min-1) for time periods of 0, 10, 20, 30 min and for 10, 20, 30 min after ceasing a 30-min infusion. After each time period, rats were then sacrificed and blood obtained. OXA was also administered at increasing doses (0, 100, 300 and 500 pmol kg-1 min-1) for 30 min and blood was obtained. Plasma OXA, insulin and glucagon levels were measured using commercially available radioimmunoassay (RIA) kits. The plasma half-life of OXA was 27.1±9.5 min. Stepwise increasing infusion rates of OXA confirmed a linear concentration-time curve and thus first-order kinetics. Its volume of distribution indicated no binding to peripheral tissues. Plasma glucagon decreased during infusion of OXA, while insulin was unaffected. Plasma OXA was raised fourfold after food intake. Thus, OXA has a longer plasma half-life than many other peptides found in the gut. This needs to be taken into account when assessing effects of OXA on biological parameters after peripheral administration.reserved.
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| 34. |
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| 35. |
- Farkas, Orsolya, et al.
(författare)
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Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 123:1-3, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has numerous different actions. Recent studies have shown that PACAP exerts neuroprotective effects not only in vitro but also in vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease and axonal injuries. Traumatic brain injury has an increasing mortality and morbidity and it evokes diffuse axonal injury which further contributes to its damaging effects. The aim of the present study was to examine the possible neuroprotective effect of PACAP in a rat model of diffuse axonal injury induced by impact acceleration. Axonal damage was assessed by immunohistochemistry using an antiserum against beta-amyloid precursor protein, a marker of altered axoplasmic transport considered as key feature in axonal injury. In these experiments, we have established the dose response curves for PACAP administration in traumatic axonal injury, demonstrating that a single post-injury intracerebroventricular injection of 100 microg PACAP significantly reduced the density of damaged, beta-amyloid precursor protein-immunoreactive axons in the corticospinal tract.
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| 36. |
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| 37. |
- Grenback, E, et al.
(författare)
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Galanin in pituitary adenomas
- 2004
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Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 117:2, s. 127-139
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Tidskriftsartikel (refereegranskat)
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| 38. |
- Holmberg, Sara K S, et al.
(författare)
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Localization of neuropeptide Y receptor Y5 mRNA in the guinea pig brain
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 117, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) has prominent stimulatory effects on food intake in virtually all animals that have been studied. In mammals, the effect is primarily mediated by receptors Y1 and Y5, which seem to contribute to different aspects of feeding behavior in guinea pigs and rats/mice. Interestingly, differences in receptor distribution among mammalian species have been reported. To get a broader perspective on the role of Y5, we describe here studies of guinea pig (Cavia porcellus), a species which due to its phylogenetic position in the mammalian radiation is an interesting complement to previous studies in rat and mouse. Guinea pig brain sections were hybridized with two 35S-labeled oligonucleotides complementary to Y5 mRNA. The highest expression levels of Y5 mRNA were observed in the hippocampus and several hypothalamic and brain stem nuclei implicated in the regulation of feeding, such as the paraventricular, arcuate and ventromedial hypothalamic nuclei. This contrasts with autoradiography studies that detected low Y5-like binding in these areas, a discrepancy observed also in rat and human. Y5 mRNA expression was also seen in the striatum, in great contrast to mouse and rat. Taken together, these data show that Y5 mRNA distribution displays some interesting species differences, but that its expression in feeding centers seems to be essentially conserved among mammals, adding further support for an important role in food intake.
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| 39. |
- Höckerfelt, U, et al.
(författare)
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Substance P (NK1) receptor in relation to substance P innervation in rat duodenum after irradiation.
- 2001
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 98:3, s. 115-26
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Tidskriftsartikel (refereegranskat)abstract
- It has previously been shown that high dose of irradiation to the rat abdomen leads to an increased level of substance P (SP) in the duodenum. In the present study the pattern of distribution of NK1 receptors (NK1-R) in rat duodenum after irradiation (5-30 Gy), was examined at the same time-point (7 days) after irradiation, comparisons being made with the distribution of SP-innervation. Immunohistochemical methods were used. In controls, NK1-R-like immunoreactivity (-LI) was detected in epithelial cells, in cells in the region of the intestinal cells of Cajal within the deep muscular plexus (ICC-DMP), in neuronal cells in the myenteric plexus, and variably in granulocytes in the mucosa. Irradiation with 5-10 Gy did not lead to obvious changes in the pattern of NK1-R-LI. After irradiation with the highest doses (25-30 Gy), the mucosa was often gravely damaged, displaying granulation tissue. No epithelial NK1-R-LI was detected in this tissue, but was present in less affected mucosa after these doses. In the region of the ICC-DMP, in the myenteric plexus, and in granulocytes, NK1-R-LI was detected also after high dose irradiation. However, the degree of NK1-R-LI in the region of the ICC-DMP was somewhat lower than seen in controls and after low doses. SP-immunoreactive nerve fibers were present in the regions where NK1-R-LI was detected. These findings support a suggestion that an increased level of SP after irradiation may contribute to the dose-dependent gastrointestinal adverse effects that occur after radiotherapy.
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| 40. |
- Jimenez, Javier, et al.
(författare)
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Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase.
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 122:2, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS). The dose–response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05–0.1 nmol/l insulin stimulated, 1–100 nmol/l had no effect, whereas concentrations ≥250 nmol/l (“high insulin”), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3′-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt2cAMP) to the incubated islets. We conclude that the positive feedback mechanisms of action of insulin are independent of islet NOS activities and remain unclear. The negative feedback action of insulin, however, can be explained by its ability to stimulate both islet ncNOS activity and the expression and activity of iNOS. The effects on iNOS are most likely transduced through phosphatidylinositol 3′-kinase and are counteracted by raising islet cyclic AMP levels.
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| 41. |
- Kölby, Lars, 1963, et al.
(författare)
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Chromogranin A as a determinant of midgut carcinoid tumour volume
- 2004
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Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 120:1-3, s. 269-73
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine (NE) tumours are characterized by their capacity to synthesize, store and release hormonal products. These substances are stored in neurosecretory vesicles together with chromogranin A (CgA). The concentration of plasma CgA in patients with NE tumours is thought to reflect the degree of NE differentiation, total tumour burden and effect of medical treatment. The aim of this study was to analyse the correlation between tumour weight and plasma CgA levels as well as the influence of treatment with a long-acting somatostatin analogue (octreotide) using nude mice with xenografted human ileal carcinoid tumours. There was a correlation between tumour weight and plasma CgA levels in all animals (p < 0.00001). In octreotide-treated mice, plasma CgA levels were significantly reduced versus untreated animals (p = 0.037). In conclusion, this study demonstrates that plasma CgA levels are closely correlated to tumour burden, and that plasma CgA is well suited for monitoring the clinical course and outcome of treatment in patients with NE tumours.
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| 42. |
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| 43. |
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| 44. |
- Monstein, Hans-Jurg, et al.
(författare)
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Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract : A polymerase chain reaction study
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 119:1-2, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: Oxytocin (OT) has a wide range of effects throughout the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. So far, the few studies performed reveal no conclusive results. The aim of this study was to examine the expression of OT and OT-receptor mRNA in the human GI tract. Material and methods: Full-thickness biopsies from all segments of the GI tract and the gallbladder were collected during operations at the Department of Surgery, Malmö University Hospital. Biopsies were taken and put immediately into fluid nitrogen and stored at -70°C until total RNA was extracted after mechanical tissue homogenization. Subsequently, poly A + mRNA was isolated from the total RNA extract using an automated nucleic acid extractor and converted into single-stranded cDNA. PCR amplifications were carried out using gene-specific OT and OT-receptor primers. The specificity of the PCR amplicons was further confirmed by Southern blot analyses using gene specific OT and OT-receptor hybridization probes. Results: Expression of OT and OT-receptor mRNA was detected in nearly all segments of the GI tract analyzed. In most of the biopsy specimens analyzed, co-expression of both OT and OT-receptor mRNA appeared to take place. Conclusion: The present study demonstrates that OT and OT-receptor mRNAs are expressed throughout the GI tract. A possible physiological and/or pathophysiological role of OT and OT-receptor expression in the human GI tract and the cellular location of its expression remain to be shown. © 2004 Elsevier B.V. All rights reserved.
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| 45. |
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| 46. |
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| 47. |
- Sergejeva, Svetlana, 1972, et al.
(författare)
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A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways in vivo
- 2004
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Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 117:2, s. 149-54
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there is no effective pharmacotherapy against exaggerated mobilisation of neutrophils in human airway diseases such as chronic obstructive pulmonary disease and asthma. We evaluated the effect of two synthetic vasoactive intestinal peptide (VIP)-like analogues on cytokine-induced neutrophil recruitment in airways in vivo. Recombinant interleukin (IL)-1 beta was administered intratracheally (i.t.) to intubated, spontaneously breathing Sprague-Dawley rats. The rats were pretreated either with a VIP synthetic peptide analogue, a pituitary adenylate cyclase-activating peptide (PACAP)-1-27 synthetic analogue, the beta(2)-adrenoceptor agonist salbutamol or vehicle, systemically or locally. Differential cell counts were performed on bronchoalveolar lavage fluid (BALf) cytospins. Effects on mean arterial blood pressure (MAP) were monitored in separate experiments. Systemic administration of the VIP analogue, the PACAP analogue and salbutamol attenuated the cytokine-induced increase in BALf neutrophil number. Local administration of the VIP analogue and salbutamol, but not the PACAP analogue, also decreased the neutrophil number in BALf. Local administration of the VIP analogue and salbutamol caused a transient decrease in MAP. Systemic or local administration of a synthetic VIP peptide analogue inhibits cytokine-induced neutrophil recruitment in airways in vivo. This action is exerted without severe, sustained cardiovascular side effects, and deserves to be further evaluated in obstructive pulmonary diseases in human.
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