Corticotropin-releasing factor. Mechanisms to inhibit gastric acid secretion in conscious dogs.

H J Lenz; S E Hester; M R Brown

doi:10.1172/JCI111788

Published March 1, 1985 - More info

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Abstract

Immunoreactivity similar to that of corticotropin-releasing factor (CRF) is found in regions of the central nervous system that modulate autonomic responses, including gastrointestinal functions. We examined the central nervous system effects of ovine CRF on gastric acid secretion in conscious dogs. Male beagle dogs (11-13 kg) were fitted with chronic intracerebroventricular cannulae and gastric fistulae. Gastric acid secretion in response to intravenously administered gastric secretory stimuli was measured by in vitro titration of gastric juice to pH 7.0 and in response to an intragastric meal by in vivo intragastric titration at pH 5.0. Plasma gastrin was determined by radioimmunoassay. CRF microinjected into the third cerebral ventricle decreased pentagastrin-stimulated gastric acid secretion for 3 h (P less than 0.01) dose-dependently (0.2-6.0 nmol X kg-1). CRF did not inhibit histamine-stimulated gastric secretion but significantly (P less than 0.01) decreased the secretory response after 2-deoxy-D-glucose for 3 h. The gastric inhibitory action of intracerebroventricularly administered CRF on pentagastrin-stimulated gastric acid secretion was completely abolished by ganglionic blockade with chlorisondamine. The opioid antagonist, naloxone, and the vasopressin antagonist, [1-deaminopenicillamine,2-(O-methyl) tyrosine,8-arginine]-vasopressin, significantly suppressed the inhibitory effect of CRF on gastric acid secretion stimulated by pentagastrin. In contrast, truncal vagotomy did not prevent the inhibition of gastric acid secretion induced by CRF. CRF (0.2-2.0 nmol X kg-1) administered intracerebroventricularly decreased gastric acid secretion stimulated by 200-ml liquid meals containing 8% peptone. CRF did not affect plasma gastrin concentrations. These results indicate that CRF microinjected into the third cerebral ventricle inhibits gastric acid secretion in conscious dogs. CRF-induced inhibition of gastric acid secretion appears to be mediated by the sympathetic nervous system and, in part, by opiate and vasopressin-dependent mechanisms.