Methiothepin attenuates gastric secretion and motility effects of vagal stimulants at the dorsal vagal complex

Add time:09/03/2019    Source:sciencedirect.com

Methiothepin, a nonselective 5-HT receptor antagonist was utilized to explore the 5-HT modulation of dorsal vagal complex–TRH (thyrotropin releasing hormone) analogue stimulated gastric functional parameters. Intracisternal methiothepin pretreatment (200, 0.1 nmol) produced significant inhibition (70%, 44%, respectively) of the TRH analogue [p-Glu-His-(3,3′-dimethyl)-Pro NH2; RX 77368 (12 pmol)]-induced gastric acid output compared to vehicle pretreatment. Intracisternal pretreatment with methysergide (nonspecific 5-HT receptor antagonist) or combined cyanopindolol (5-HT1A and 1B receptor antagonist)+ritanserin (receptor antagonist of the 5-HT2 family) did not alter the dorsal vagal complex–RX 77368 response. Unilateral dorsal vagal complex pretreatment with methiothepin (50 nmol/50 nl) attenuated ipsilateral dorsal vagal complex–TRH analog (12 pmol) induced gastric secretory response by 57%. The gastric secretagogue response to stimulation of the raphe obscurus (mediated by TRH release into the dorsal vagal complex) was inhibited 50% by pretreatment with intracisternal dorsal medullary methiothepin (0.1 nmol/10 μl). Intracisternal methiothepin (200 nmol/20 μl) also attenuated (a) dorsal vagal complex–glutamate (60 nmol/30 nl) stimulated gastric acid secretion and (b) gastric motility stimulated by dorsal vagal complex–RX 77368 (12 pmol/30 nl). The data suggest that other properties of methiothepin, alone or in addition to its 5-HT receptor antagonist effect, mediate its inhibitory actions at the dorsal vagal complex.

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