title: Characterization of the murine pancreatic receptor for gastrin releasing peptide and bombesin.
abstract: The murine pancreatic receptor for bombesin and gastrin releasing peptide (GRP) has been characterized. Analysis of the binding of 125I-GRP to membranes indicates a single class of sites (10(-13) mol/mg protein) with Kd of 43 pM. A 70 kDa membrane protein was cross-linked to 125I-GRP by bis(sulfosuccinimidyl) suberate; labeling was blocked by GRP, GRP (14-27), AcGRP(20-27), GRP(18-27), bombesin and ranatensin, was partially blocked by [Leu13 psi (CH2NH)Leu14]bombesin and was unaffected by GRP(21-27) and GRP(1-16). The IC50 values for the competitive displacement of 125I-GRP from intact membranes by these peptides were similar to those obtained by the cross-linking experiments showing that the 70 kDa protein is the GRP receptor. The GRP receptor is G-protein coupled; divalent cations are required for high-affinity binding and nonhydrolyzable GTP analogs decrease receptor affinity. In minced pancreas, GRP caused a dose-dependent increase in inositol phosphates implicating phospholipase C in signal transduction. We suggest that the murine pancreatic receptor for bombesin/GRP is a 70 kDa membrane protein, is associated with a G-protein and stimulates phosphatidylinositol turnover.
authors.affiliation: Merrell Dow Research Institute, Cincinnati, OH 45215-6300.
authors.forename: B O
authors.initials: BO
authors.lastname: Fanger
authors.forename: A C
authors.initials: AC
authors.lastname: Wade
authors.forename: A D
authors.initials: AD
authors.lastname: Cardin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000378:metabolism*; D007294:Inositol / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011122:Polyphosphates / Q000494:pharmacology; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D004075:Diglycerides; D005755:Gastrins; D010455:Peptides; D011122:Polyphosphates; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D007294:Inositol; D019886:Gastrin-Releasing Peptide; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; C005692:triphosphoric acid; D001839:Bombesin