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Modulation of gastrin‐releasing peptide (GRP) receptors in insulin secreting cells
Author(s) -
Kloss Hendrik,
Wahl Martin A.,
Neye Holger,
Verspohl Eugen J.
Publication year - 1999
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/(sici)1099-0844(199912)17:4<229::aid-cbf834>3.0.co;2-l
Subject(s) - gastrin releasing peptide , medicine , receptor , bombesin , pancreatic islets , endocrinology , chemistry , peptide , calcitonin , peptide hormone , cholecystokinin , calcitonin gene related peptide , binding site , pancreatic polypeptide , insulin , neuropeptide , biochemistry , biology , islet , glucagon
Gastrin‐releasing peptide (GRP) receptors are present in pancreatic islets, though their regulation is unknown except for homologous desensitization. The modulation of binding of GRP to mouse pancreatic islets and INS‐1 cells was studied. At 60 min (steady‐state), total binding of [ 125 I‐Tyr 15 ] GRP was 1·62 per cent of total radioactivity per 50 islets; non‐specific binding (presence of 1 m M unlabelled GRP(1‐27)) was 0·05 to 0·61 per cent of total radioactivity. A preincubation with 1000 n m cholecystokinin (CCK 8 ) or with 1000 n m glucose‐dependent insulinotropic peptide (GIP) augmented the number of GRP binding sites but not their affinity. [ 125 I‐Tyr 15 ]GRP binding to INS‐1 cells was saturable (90 min) and specific with respect to compounds that are not chemically related to GRP (e.g. calcitonin gene‐regulated peptide—CGRP and atrial natriuretic peptide—ANP). Displacement studies showed one binding site with a K d of 0·39 n m and a B max of 13·2 fmoles mg −1 protein. When the cells were pretreated for 24 h with 10 n m GIP or CCK 8 , only GIP but not CCK 8 increased the B max of the GRP binding site. The affinity (K d ) was not changed by either compound. This effect of GIP pretreatment was not affected by downregulating PKC by TPA (phorbol ester; long‐term pretreatment). These data indicate that: (1) specific binding sites for GRP are present in mouse pancreatic islets and INS‐1 cells; (2) the GRP binding is upregulated by GIP in both islets and INS‐1 cells and additionally by CCK 8 , albeit only in islets; and (3) PKC does not seem to be involved in the up‐regulation process. Thus a positive interplay between both the incretins GIP and CCK 8 and the neurotransmitter GRP is obvious. Copyright © 1999 John Wiley & Sons, Ltd.