title: Mechanism of gastric alkaline response in the stomach after damage. Roles of nitric oxide and prostaglandins.
abstract: The gastric mucosa responds to hypertonic NaCl by significantly decreasing acid secretion. We examined the role of nitric oxide (NO) in this phenomenon in comparison with endogenous prostaglandins (PGs). A rat stomach was mounted in an ex vivo chamber, perfused with saline, and the potential difference (PD), pH, and acid/alkaline responses were measured before and after the application of hypertonic NaCl (1 mol/liter) with or without pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; an inhibitor of NO biosynthesis) or indomethacin (a cyclooxygenase inhibitor). NaCl at 1 M caused a PD reduction, a decrease in acid secretion, and an increase in luminal HCO3-. Prior administration of L-NAME (5 mg/kg, intravenously) as well as indomethacin (5 mg/kg, subcutaneously) did not affect PD and HCO3- responses, but significantly attenuated the inhibitory effect of 1 M NaCl on acid secretion, although the effect of L-NAME was more potent when compared to indomethacin. This effect of L-NAME was antagonized by the simultaneous administration of L-arginine but not by D-arginine (200 mg/kg, intravenously), whereas the effect of indomethacin was completely reversed by PGE2 (100 micrograms/kg, intravenously). The histamine-stimulated acid secretion in the normal stomach was significantly decreased by nitroprusside (the exogenous NO donor; 4 mg/kg, intravenously) and PGE2, but not by either L-NAME or indomethacin. These results suggest that in addition to PGs, NO is involved in the mechanism of the gastric alkaline response after damage with 1 M NaCl. Irritation of the gastric mucosa by hypertonic NaCl may release endogenous NO and PGs, both of which in turn inhibit acid secretion and unmask luminal alkalinization due to HCO3- flux in the damaged portion.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Okabe
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic
chemical_list: D001639:Bicarbonates; D012462:Saline Solution, Hypertonic; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D015232:Dinoprostone; D009853:Omeprazole; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin