5-HT in DVC: disparate effects on TRH analogue-stimulated gastric acid secretion, motility, and cytoprotection.

Convergent evidence suggests that thyrotropin-releasing hormone (TRH) is a principal regulator of several vagally mediated gastric responses. Serotonin (5-HT) interacts with TRH in the dorsal vagal complex (DVC) to augment gastric acid secretory responses. This study investigated the ability of 5-HT to alter other gastric responses mediated by TRH administration into the DVC. Co-injection of 5-HT (7.9 pmol) and the TRH analogue RX-77368 (0.66 pmol) produced a 117% enhancement in 1-h gastric acid output compared with rats treated with RX-77368 (0.66 pmol) alone into the DVC. In contrast, coadministration of RX-77368 (4 pmol) with various doses of 5-HT (0.0048-480 pmol) was ineffective in significantly altering stimulation of gastric antral motility produced by RX-77368 (4 pmol) alone. The effect of a lower dose of DVC RX-77368 (0.66 pmol) on gastric motility was also not changed by 5-HT coadministration. Moreover, the cytoprotective effect of DVC RX-77368 (1.5 pmol) on oral ethanol-induced gastric mucosal lesions was reversed by 5-HT coadministration (54 or 18 pmol). The results suggest that activation of 5-HT receptors in the DVC can augment, not affect, and attenuate DVC TRH analogue-stimulated gastric acid secretion, antral motility, and cytoprotection, respectively.