CNS actions of calcitonin gene-related peptide on gastric acid secretion in conscious dogs.

To determine the mechanisms of action of calcitonin gene-related peptide (CGRP) in inhibiting gastric acid secretion, we studied awake male beagle dogs fitted with a chronic intracerebroventricular cannula and a gastric fistula. Synthetic rat CGRP (10 pmol/kg to 10 nmol/kg) given intracerebroventricularly or intravenously significantly inhibited pentagastrin-stimulated gastric acid secretion. CGRP (1 nmol/kg) given intracerebroventricularly decreased acid secretion stimulated by 2-deoxy-D-glucose but not by histamine. CGRP-(1-14), [Tyr23]CGRP-(23-37), and [acetamidomethyl-Cys2,7]CGRP, the linear peptide molecule devoid of the disulfide bridge, did not affect gastric secretion. Ganglionic blockade with chlorisondamine, a vasopressin antagonist, naloxone, and truncal vagotomy did not abolish the gastric inhibitory action of CGRP given intracerebroventricularly. CGRP administered intracerebroventricularly and intravenously decreased gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% peptone meal. It is concluded that CGRP given intracerebroventricularly or intravenously inhibits gastric acid secretion in conscious dogs; the intact molecule appears to be necessary for biological activity; and inhibition of gastric acid secretion by CGRP in the dog is not mediated by the autonomic nervous system or vasopressin-, opiate-, or gastrin-dependent pathways.