Inhibition of gastric acid secretion and ulcers by calcitonin [correction of calciton] gene-related peptide.
A central action of CGRP to inhibit gastric acid secretion, demonstrated in rats and dogs, is mediated at least in rats through modulation of parasympathetic outflow to the stomach. The centrally mediated protective effects of CGRP against 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 flow 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 central regulation of gastric function. Peripheral injection of CGRP is well established to inhibit acid secretion 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. The rich innervation of the stomach with CGRP-like immunoreactivity, which forms the major component of gastric sensory fibers, along with peptide release by sensory stimulation and potent actions on gastric secretions suggests a role of the peptide in the regulation of gastric function.
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Department of Medicine and Brain Research Institute, University of California, Los Angeles 90073.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D051381:Rats; D013276:Stomach Ulcer / Q000517:prevention & control*
D015740:Calcitonin Gene-Related Peptide