Characterization of specific calcitonin gene related peptide receptors present in hamster pancreatic β cells
Author:
Barakat A.1, Rosselin G.1, Marie J.-C.1
Affiliation:
1. Institut National de la Santé et de la Recherche Médicale U.55, Hôpital Saint-Antoine, 75571 Paris Cedex 12, France
Abstract
Calcitonin gene-related peptide (CGRP) shares about 46% and 20% amino acid sequence homology with islet amyloid polypeptide (IAPP) and salmon calcitonin (sCT). We investigated whether these related peptides could cross-react with the specific binding of 125I-[His]hCGRP I to the CGRP receptor in hamster insulinoma cell membranes. A rapid dissociation of membrane bound 125I-[His]hCGRP I could be induced in the presence of 1 μM chicken CGRP (cCGRP). The specific 125I-[His]hCGRP I binding was inhibited by the related peptides and their half-maximal inhibitory concentrations (IC50) were: cCGRP (0.1 nM), rat CGRP I and human CGRP I and II (1.0–2.0 nM), fragment of hCGRP I (8–37) (150 nM), human IAPP (440 nM). The non-amidated form of hIAPP; human diabetes-associated peptide (hDAP) did not inhibit the binding of 125I-[His]hCGRP I and sCT was only effective at a high concentration (1 μM). Binding of 125I-[His]hCGRP I was dose dependently inhibited by guanosine-5′-O-(3-thiotriphosphate) or (GTPγS) and a 70% reduction of binding was obtained with 0.1 mM GTPγS. The IC50 value of cCGRP (0.1 nM) was increased 100-fold in the presence of 0.1 mM GTPγS. Human CGRP I and cCGRP at 2.5 μM did not stimulate the activity of hamster insulinoma cell membranes adenylate cyclase, while glucagon (1 μM) induced a 2-fold increase. Thus, specific CGRP receptors present in hamster β cells are associated with G protein (s) and IAPP can interact with these receptors. These results and the observation that cCGRP and hCGRP I did not influence adenylate cyclase activity provide further evidence for CGRP receptor subtypes.
Publisher
Portland Press Ltd.
Subject
Cell Biology,Molecular Biology,Biochemistry,Biophysics
Reference37 articles.
1. Amara, S. G., Jonas, V., Rosenfeld, M. G., Ong, E. S. and Evans, R. M. (1982) Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products.Nature,298:240?244. 2. Rosenfeld, M. G., Mermod, J. J., Amara, S. G., Swanson, L. W., Sawchenko, P. E., Rivier, J., Vale, W. W. and Evans, R. M. (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing.Nature,304:129?135. 3. Wimalawansa, S. J., Emson, P. C. and MacIntyre, I. (1987) Regional distribution of calcitonin gene-related peptide and its specific binding sites in rats with particular reference to the nervous system.Neuroendocrinology,46:131?136. 4. Mulderry, P. K., Ghatei, M. A., Rodrigo, J., Allen, J. M. Rosenfeld, M. G., Polak, J. M. and Bloom, S. R. (1985) Calcitonin gene-related peptide in cardiovascular tissues of the rat.Neuroscience,14:947?954. 5. Pettersson, M., Ahrén, B., Böttcher, G., and Sundler, F. (1986) Calcitonin gene-related peptide: Occurrence in pancreatic islets in the mouse and the rat and inhibition of insulin secretion in the mouse.Endocrinology,119:865?869.
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. The effects of CGRP in vascular tissue - Classical vasodilation, shadowed effects and systemic dilemmas;European Journal of Pharmacology;2020-08 2. Effects on Different Peptide Hormones;Drug Discovery and Evaluation: Pharmacological Assays;2016 3. Effects on Different Peptide Hormones;Drug Discovery and Evaluation: Pharmacological Assays;2015 4. Endocrinology;Drug Discovery and Evaluation;2007 5. Endocrinology1;Drug Discovery and Evaluation;2002
|
|