Intracisternal TRH analogue RX 77368 stimulates gastric histamine release in rats

The influence of intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analogue RX 77368 on histamine levels in gastric secretion, interstitial fluid of the fundic submucosa, and portal hepatic circulation was investigated in rats. Intracisternal injection of RX 77368 (10-300 ng) induced a dose-related increase in histamine and acid output measured in the gastric secretion of pylorus-ligated, conscious rats. Intracisternal RX 77368 (300 ng) induced within 20 min a significant twofold histamine increase in interstitial fluid sampled from dialysis fibers implanted into the fundic submucosa. Histamine levels in the hepatic portal circulation were also dose dependently increased by RX 77368 injected intracisternally (30-100 ng), whereas intravenous infusion of RX 77368 (300 ng/30 min) did not significantly modify portal histamine levels. Bilateral cervical vagotomy or atropine pretreatment prevented intracisternal RX 77368-induced rise in hepatic portal levels of histamine, whereas purified gastrin monoclonal antibody 9303, injected at a dose blocking gastrin-stimulated acid secretion, had no effect. These results indicate that RX 77368 acts in the brain to increase gastric histamine secretion through vagal-dependent, muscarinic, nongastrin-mediated mechanisms and suggest a possible role of medullary TRH in the vagal regulation of gastric histamine secretion.