Corticotropin-releasing factor acts centrally to suppress stimulated gastric contractility in the rat.

The effects of intracisternal (i.c.) and intravenous (i.v.) administration of corticotropin-releasing factor (CRF) on gastric contractility stimulated by i.c. injection of the TRH analog RX77368 [p-Glu-His-(3,3'-dimethyl)-Pro-NH2], 2-deoxy-D-glucose (2DG) and i.v. infusion of carbachol were evaluated in rats under urethane anesthesia. Gastric contractility was monitored using acutely implanted extraluminal force transducers sutured to the corpus of the stomach. I.c. injection of CRF (6.3-210 pmol) resulted in a dose dependent suppression of gastric contractility stimulated by RX77368 (260 pmol) and 2DG (6 mg). Gastric inhibitory response to i.c. CRF was rapid in onset and lasted at least 45 min. Carbachol (200 mg/kg/h)-induced stimulation of gastric contractility was not modified by i.c. injection of CRF. The stimulation of contractility caused by both i.v. carbachol and i.c. 2DG were completely inhibited by atropine (1 mg/kg, i.v.). CRF (210 pmol) given i.v. suppressed RX77368-stimulated gastric contractions, but was less than 1/10 as potent as administered i.c. I.v. CRF (210 pmol) did not alter 2DG- or carbachol-induced gastric contractions. These results demonstrate that the i.c. administration of CRF acts within the brain to inhibit gastric contractility elicited by vagus-dependent mechanisms.