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.

Thyrotropin-releasing hormone (TRH) acts centrally to stimulate gastric contractility in rats.

Changes in gastric contractility induced by intracisternal (ic) injection of thyrotropin-releasing hormone (TRH) or a stable TRH analog, RX77368 [p-Glu-His-(3,3'-dimethyl)-Pro NH2] were investigated in 24 h fasted-conscious rats. Gastric contractility was monitored using chronically implanted extraluminal force transducers sutured to the corpus. Response elicited by a standard meal was used as a physiologic standard. Intracisternal injection of TRH (1 microgram) or RX77368 (100 ng), unlike saline, stimulated high amplitude gastric contractions. The stimulation of gastric contractions induced by ic RX77368 was dose dependent (3-100 ng), rapid in onset, long lasting and not mimicked by the intravenous route of administration. Atropine (0.1 mg/kg) partially antagonized and vagotomy totally blocked the RX77368 (100 ng, ic)-induced stimulation of gastric contractility. These results demonstrated that TRH or RX77368 acts within the brain to elicit potent contractions of the stomach; TRH action appears vagally mediated probably through cholinergic mechanism.

Corticotropin-releasing factor acts on the brain to reduce gastric contractility.

Various stressors (cold restraint, electric shock, etc.) applied to rats increase gastric contractility and are associated with gastric erosions. Intracisternal (i.c.) thyrotropin-releasing hormone (TRH) increases contractility, gastric acid secretion and the incidence of erosion formation. Corticotropin-releasing hormone (CRF) is released by stress, and acting centrally produces autonomic and endocrine changes. We have studied the role of i.c. CRF on gastric contractility in anesthetized rats (n = 6). Contractility was measured by extraluminal force transducers sutured to the gastric corpus. Frequency, amplitude of contractions and a motility index were analyzed by computer. Baseline measures, after recovery from surgery were obtained in 24-hour fasted rats. Contractility was stimulated by intravenous carbachol (100 mg/kg/h) or i.c. injection of the TRH analog, RX 77368. Contractility thus induced was inhibited by intravenous atropine (1 mg/kg). CRF (30-1,000 ng i.c.) produced a dose-dependent suppression of RX 77368 (p less than 0.05) but had no effect on that induced by intravenous carbachol; saline i.c. had none either. Intravenous CRF was 1/10th as potent in suppressing contractions produced by i.c. RX 77368. Diminution of gastric contractions after i.c. CRF (1 mg) occurred within 5 min of administration, and lasted for at least 60 min. These data show that i.c. CRF injection acts centrally to inhibit gastric contractions stimulated centrally (i.e. by i.c. RX 77368) but not peripherally (i.e. by carbachol), and by inference reduces the risk of erosion formation induced by some stressors.