Vagal regulation of gastric prostaglandin E2 release by central TRH in rats.

The central action of the stable thyrotropin-releasing hormone (TRH) analogue, RX 77368, to induce vagal release of gastric prostaglandin E2 (PGE2) was investigated in urethan-anesthetized rats. Intracisternal RX 77368 (1.5-1,000 ng) dose dependently increased gastric PGE2 levels measured for 3 h in the perfusate of dialysis fibers implanted into the corpus submucosa. RX 77368 injected intravenously (1,000 ng) had no effect. The stimulatory action of RX 77368 (1.5 ng) on gastric PGE2 release was blocked by indomethacin and bilateral cervical vagotomy. Omeprazole did not alter the PGE2 response to 3 ng of RX 77368 and reduced by 39% PGE2 release induced by the 1,000-ng dose. RX 77368 (1.5 ng) by itself did not influence acid secretion but increased acid output to 117 +/- 18 mumol/2 h in indomethacin-pretreated rats. Indomethacin also increased by 97% the acid response to the 3-ng dose of RX 77368, but the effect of a maximal effective dose of RX 77368 was not modified. These results indicate that RX 77368 acts in the brain to induce a vagal-dependent stimulation of gastric PGE2 secretion which is biologically active to reduce the acid response to submaximal doses of TRH analogue. These data suggest a possible role of medullary TRH in the central vagal regulation of gastric PGE2 release.