Inhibitory effect of N(omega)-nitro-L-arginine on gastric secretion induced by secretagogues and vagal stimulation in the isolated stomach.
The involvement of endogenous nitric oxide (NO) in the control of gastric acid secretion induced by some secretagogues was studied in the mouse isolated whole stomach. The gastric acid secretion induced by McNeil A-343 [4-[[[(3-chlorophenyl)amino]carbonyl]oxy]-N,N,N-trimethyl-2-butyn- 1-aminium chloride], a muscarinic M1 receptor agonist, pentagastrin or electrical vagus nerve stimulation was markedly inhibited by pretreatment with the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA). This inhibitory effect of L-NNA was reversed by L-arginine, but not by D-arginine. Histamine-induced gastric acid secretion was not influenced by treatment with L-NNA. Famotidine completely inhibited the gastric acid secretion induced by McNeil A-343, pentagastrin or electrical vagus nerve stimulation, showing that these stimulations induced gastric acid secretion mainly through histamine release from histamine-containing cells in the gastric mucosa. Moreover, the pentagastrin- and bethanechol-induced histamine release from gastric mucosal cells was significantly inhibited by L-NNA. The NO donor, sodium nitroprusside, at a concentration not affecting histamine-induced gastric acid secretion, increased the acid secretory response, and this response was inhibited by famotidine. These results suggest that endogenous NO is involved in the gastric acid secretion via histamine release from histamine-containing cells.
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
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Hasebe
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Horie
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Yano
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Watanabe
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010418:Pentagastrin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D019335:Nitroarginine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D006632:Histamine; D019001:Nitric Oxide Synthase; D010418:Pentagastrin