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 microM(-1) x mM) inhibited the gastric acid secretion induced by histamine (500 microM) in a concentration-dependent manner. In addition, nitroprusside abolished the acid secretion induced by bethanechol (100 microM) and by electrical stimulation (10 Hz) of the vagus nerve. On the other hand, nitroprusside, 75 microM, which did not affect the acid secretion induced by histamine, itself elicited an increase in acid secretion. The acid secretion induced by 75 microM nitroprusside was inhibited by 10 microM famotidine, a histamine H2 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.
Hasebe
K
K
Laboratory of Chemical Pharmacology, Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, 263-8522, Chiba, Japan.
Horie
S
S
Komasaka
M
M
Yano
S
S
Watanabe
K
K
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D015738:Famotidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000294:innervation; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D018723:Bethanechol; D009599:Nitroprusside; D015738:Famotidine; D006632:Histamine