Stimulatory effects of nitric oxide donors on gastric acid secretion in isolated mouse stomach

We previously reported on the stimulatory role of endogenous nitric oxide (NO) in gastric acid secretion. In the present study, we investigated the effects of NO donors on acid secretion in isolated mouse stomach. Nitroprusside (100 muM-1 mM) inhibited the gastric acid secretion induced by histamine (500 muM) in a concentration-dependent manner. In addition, nitroprusside abolished the acid secretion induced by bethanechol (100 muM) and by electrical stimulation (10 Hz) of the vagus nerve. On the other hand, nitroprusside, 75 muM, which did not affect the acid secretion induced by histamine, itself elicited an increase in acid secretion. The acid secretion induced by 75 ELM nitroprusside was inhibited by 10 muM famotidine, a histamine H-2 receptor antagonist. These results suggest that NO donors at high doses act on gastric parietal cells, resulting in inhibition of the stimulated acid secretion, and, at lower doses, facilitate histamine release from histamine-containing cells, leading to the increased acid secretion. (C) 2001 Elsevier Science B.V. All rights reserved.