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AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 5 760-G766, Copyright © 1990 by American Physiological Society
ARTICLES |
S. Fiorucci and K. E. McArthur
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75216.
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.
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S. Fiorucci, E. Distrutti, B. Federici, B. Palazzetti, M. Baldoni, A. Morelli, and G. Cirino PAR-2 modulates pepsinogen secretion from gastric-isolated chief cells Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285(3): G611 - G620. [Abstract] [Full Text] [PDF] |
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