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OBJECTIVE Histamine plays an important role in gastric function, and the histaminergic system is involved in the regulation of neuropeptides and gastric acid secretion. METHODS We investigated the effect of histamine and histamine receptor antagonist (HRA) on the intraluminal secretion of thyrotropin-releasing hormone (TRH) and somatostatin (SOM) using a rat luminal perfusion model. RESULTS Intravenous administration of histamine caused an increase in TRH secretion and a decrease in SOM secretion preceding a decrease in pH in the perfusate. When the total contents of TRH and SOM in the perfusate were calculated after administration of histamine, the effect of histamine was found to be dose-dependent in both neuropeptide secretions. Under basal conditions, neither H1RA, H2RA, nor H3RA caused changes in TRH secretion into the perfusate. In contrast, H2RA and H3RA yielded an increase in basal SOM secretion. When administered before the injection of histamine, H2RA caused a complete inhibition of histamine-induced changes in TRH and SOM secretion. Preadministration of H3RA also induced a weak but significant inhibition of the changes in neuropeptide secretion. CONCLUSIONS It was concluded that paracrine pathways do exist among histamine, TRH, and SOM in the regulation of gastric acid secretion.
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