Low doses of TRH analogue act in the dorsal motor nucleus to induce gastric protection in rats.

Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E2 (PGE2) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE2-, CGRP-, and nitric oxide-dependent mechanisms.