AJP - Gastrointestinal and Liver Physiology, Vol 250, Issue 6 742-G748, Copyright © 1986 by American Physiological Society
CNS actions of calcitonin gene-related peptide on gastric acid secretion in conscious dogs
H. J. Lenz, S. E. Hester, R. P. Saik and M. R. Brown
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.
