Gastrin-releasing peptide directly releases pepsinogen from guinea pig chief cells.
Gastrin-releasing peptide (GRP) and bombesin can stimulate pepsinogen release by both gastrin-dependent and -independent mechanisms. Using isolated guinea pig gastric chief cells, we determined that GRP can act directly on the guinea pig chief cell to cause pepsinogen release. GRP and bombesin stimulated a 2.5- to 3-fold increase in pepsinogen release above basal release. Substance P also stimulated a small but significant increase in pepsinogen release. No gastrin immunoreactivity was detected in the supernatants of cells stimulated with up to 1 microM GRP or bombesin or 1 mM carbachol. GRP-stimulated pepsinogen release was completely inhibited by GRP/bombesin receptor agonists as well as substance P receptor antagonist but not by antagonists to receptors for gastrin, the octapeptide of cholecystokinin (CCK-8), secretin, vasoactive intestinal peptide (VIP), or muscarinic agents. Substance P-stimulated pepsinogen release was completely inhibited by substance P receptor antagonist but not by GRP/bombesin receptor antagonists. An additive effect on pepsinogen release was seen when GRP was combined with maximally effective concentrations of adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (VIP, secretin, 8-BrcAMP) but not with calcium-mediated agents (carbachol, CCK-8, gastrin). These results indicate that GRP can directly stimulate pepsinogen release from guinea pig chief cells by a specific GRP receptor that mobilizes intracellular calcium.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75216.
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Fiorucci
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McArthur
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D010435:Pepsinogens / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005755:Gastrins; D005768:Gastrointestinal Hormones; D010435:Pepsinogens; D010455:Peptides; D012633:Secretin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D019886:Gastrin-Releasing Peptide; D002217:Carbachol; D012844:Sincalide; D001839:Bombesin