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Modulation of gastrin‐releasing peptide (GRP) receptors in insulin secreting cells

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 [125I‐Tyr15] GRP was 1·62 per cent of total radioactivity per 50 islets; non‐specific binding (presence of 1 mM unlabelled GRP(1‐27)) was 0·05 to 0·61 per cent of total radioactivity. A preincubation with 1000 nm cholecystokinin (CCK8) or with 1000 nm glucose‐dependent insulinotropic peptide (GIP) augmented the number of GRP binding sites but not their affinity. [125I‐Tyr15]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 Kd of 0·39 nm and a Bmax of 13·2 fmoles mg−1 protein. When the cells were pretreated for 24 h with 10 nm GIP or CCK8, only GIP but not CCK8 increased the Bmax of the GRP binding site. The affinity (Kd) 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 CCK8 , 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 CCK8 and the neurotransmitter GRP is obvious. Copyright © 1999 John Wiley & Sons, Ltd.