Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats.
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.
Hasebe
Ko
K
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan. Ko_Hasebe@nts.toray.co.jp
Horie
Syunji
S
Noji
Tohru
T
Watanabe
Kazuo
K
Yano
Shingo
S
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
D018723:Bethanechol; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D003847:Deoxyglucose