Central and peripheral actions of calcitonin gene-related peptide on gastric secretory and motor function.
CGRP exerts a potent central action to inhibit gastric acid secretion in rats and dogs and gastric emptying, contractility and ulcer formation in rats. The site of action to inhibit acid secretion has been localized in the dorsal vagal complex. The inhibition of acid secretion is related primarily to the decrease in vagal efferent activity whereas the inhibition of gastric motor functions involves increases in sympathetic outflow. The central action of CGRP to prevent ethanol-induced lesions is unique to this peptide and not shared by other centrally acting inhibitors of gastric function. It may be related to the increase in gastric mucosal blood induced by central CGRP. The presence of CGRP-like immunoreactivity and receptors in medullary nuclei receiving visceral information and influencing vagal outflow suggests a possible role of the peptide in the vagal regulation of gastric secretion. Peripheral injection of CGRP also inhibits acid secretion when administered peripherally in rats, dogs, rabbits and humans. Its antisecretory effect is unlikely to be related to a direct action on the parietal cells. It involves specific and marked release of gastric somatostatin through an interaction with CGRP receptors characterized on D cells and coupled with cAMP. In addition, CGRP induces a decrease in acetylcholine transmission in the enteric nervous system which may contribute to the inhibition of acid. Peripheral CGRP inhibits gastric emptying and motility by a direct action on smooth muscles through receptors linked with cAMP. The release of CGRP from spinal afferents innervating the stomach in response to stimulation of capsaicin-sensitive fibers suggests a role of the peptide in the regulation of gastric function.
Taché
Y
Y
Center for Ulcer Research and Education, VA Wadsworth Medical Center, Los Angeles, California.
Raybould
H
H
Wei
J Y
JY
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology* / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans
D015740:Calcitonin Gene-Related Peptide