title: Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats.
abstract: We previously reported the stimulatory effect of endogenous nitric oxide (NO) on gastric acid secretion in the isolated mouse whole stomach and histamine release from gastric histamine-containing cells. In the present study, we investigated the effects of endogenous and exogenous NO on gastric acid secretion in urethane-anesthetized rats. Acid secretion was studied in gastric-cannulated rats stimulated with several secretagogues under urethane anesthesia. The acid secretory response to the muscarinic receptor agonist bethanechol (2 mg/kg, s.c.), the cholecystokinin(2) receptor agonist pentagastrin (20 microg/kg, s.c.) or the centrally acting secretagogue 2-deoxy-D-glucose (200 mg/kg, i.v.) was dose-dependently inhibited by the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 or 50 mg/kg, i.v.). This inhibitory effect of L-NNA was reversed by a substrate of NO synthase, L-arginine (200 mg/kg, i.v.), but not by D-arginine. The histamine H(2) receptor antagonist famotidine (1 mg/kg, i.v.) completely inhibited the acid secretory response to bethanechol, pentagastrin or 2-deoxy-D-glucose, showing that all of these secretagogues induced gastric acid secretion mainly through histamine release from gastric enterochromaffin-like cells (ECL cells). On the other hand, histamine (10 mg/kg, s.c.)-induced gastric acid secretion was not inhibited by pretreatment with L-NNA. The NO donor sodium nitroprusside (0.3-3 mg/kg, i.v.) also dose-dependently induced an increase in acid secretion. The sodium nitroprusside-induced gastric acid secretion was significantly inhibited by famotidine or by the soluble guanylate cyclase inhibitor methylene blue (50 mg/kg, i.v.). These results suggest that NO is involved in the gastric acid secretion mediated by histamine release from gastric ECL cells.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan. Ko_Hasebe@nts.toray.co.jp
authors.forename: Ko
authors.initials: K
authors.lastname: Hasebe
authors.forename: Syunji
authors.initials: S
authors.lastname: Horie
authors.forename: Tohru
authors.initials: T
authors.lastname: Noji
authors.forename: Kazuo
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shingo
authors.initials: S
authors.lastname: Yano
mesh_terms: D000758:Anesthesia; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
chemical_list: D018723:Bethanechol; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D003847:Deoxyglucose