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 anex 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 HCO −3 . Prior administration ofl-NAME (5 mg/kg, intravenously) as well as indomethacin (5 mg/kg, subcutaneously) did not affect PD and HCO −3 responses, but significantly attenuated the inhibitory effect of 1 M NaCl on acid secretion, although the effect ofl-NAME was more potent when compared to indomethacin. This effect ofl-NAME was antagonized by the simultaneous administration ofl-arginine but not byd-arginine (200 mg/kg, intravenously), whereas the effect of indomethacin was completely reversed by PGE2 (100 µg/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 eitherl-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 HCO −3 flux in the damaged portion.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Swierczek JS, Konturek SJ: Gastric alkaline response to mucosa-damaging agents; effect of 16,16-dimethyl prostaglandin E2. Am J Physiol 241:G509-G515, 1981
Svanes K, Ito S, Takeuchi K, Silen W: Restitution of the surface epithelium of thein vitro frog gastric mucosa after damage with hyperosmolar sodium chloride; morphologic and physiologic characteristics. Gastroenterology 82:1409–1426, 1982
Nobuhara Y, Takeuchi K: Possible role of endogenous prostaglandins in alkaline response in rat gastric mucosa damaged by hypertonic NaCl. Dig Dis Sci 29:1142–1147, 1984
Takeuchi K, Ueki S, Tanaka H: Endogenous prostaglandins in gastric alkaline response in the rat stomach after damage. Am J Physiol 250:G842-G849, 1986
Takeuchi K, Ohno T, Okabe S: Irritative and protective activity of mild irritants in rat stomach. Dig Dis Sci 32:889–896, 1987
Furchgott RF: The role of endothelium in the response of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol 24:175–197, 1984
Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142, 1991
Pique JM, Whittle BJR, Espluges JV: The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation. Eur J Pharmacol 174:293–296, 1989
T Lippe I, Holzer P: Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperemia due to acid back-diffusion. Br J Pharmacol 105:708–714, 1992
Martinez-Cuesta MA, Barrachina MD, Pique JM, Whittle BJR, Esplugues JV: The role of nitric oxide and platelet-activating factor in the inhibition by endotoxin of pentagastrin-stimulated gastric acid secretion. Eur J Pharmacol 218:351–354, 1992
Takeuchi K, Ohuchi T, Miyake H, Okabe S: Stimulation by nitric oxide synthase inhibitors of gastric and duodenal HCO −3 secretion in rats. J Pharmacol Exp Ther 266:1512–1519, 1993
Whittle BJR, Lopes-Bermonte J, Moncada S: Regulation of gastric mucosal integrity by endogenous nitric oxide: Interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol 99:607–611, 1991
Takeuchi K, Ohuchi T, Okabe S: Endogenous nitric oxide in gastric alkaline response in the rat stomach after damage. Gastroenterology 106:367–374, 1994
Takeuchi K, Ishihara Y, Okada M, Niida H, Okabe S: A continuous monitoring of mucosal integrity and secretory activity in rat stomach; a preparation using a lucite chamber. Jpn J Pharmacol 49:235–244, 1989
Takeuchi K, Ueshima K, Matsumoto J, Okabe S: Role of capsaicin-sensitive sensory nerves in acid-induced bicarbonate secretion in rat stomach. Dig Dis Sci 37:737–743, 1992
Davenport HW: Fluid produced by the gastric mucosa during damage by acetic and salicylic acids. Gastroenterology 50:487–499, 1966
Kitagawa H, Ikejiri T, Nishiwaki H, Kohei H: Endothelium-dependent adaptive gastric protection. Jpn J Pharmacol 58(suppl 1):131, 1992 (abstract)
Robert A: Prostaglandins in the gastrointestinal tract.In Physiology of the Gastrointestinal Tract. LR Johnson, J Christensen, MI Grossman, ED Jacobson, SG Schultz (eds). New York, Raven Press, 1981, pp 1407–1434
Takeuchi K, Ohuchi T, Okabe S: Nitric oxide mediates inhibition of gastric acid secretion in the damaged stomach: Interaction with endogenous prostaglandins. Gastroenterology 106:A-1692, 1994 (abstract)
Tepperman BL, Brown JF, Whittle BJR: Nitric oxide synthase induction and intestinal epithelial cell viability in rats. Am J Physiol 265:G214-G218, 1993
Takeuchi K, Yamakuni H, Nobuhara Y, Okabe S: Functional and morphologic alterations in the rat stomach following exposure to hypertonic NaCl solutions. Jpn J Pharmacol 42:539–548, 1986
Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P: Nitric oxide activates cyclooxygenase enzyme. Proc Natl Acad Sci USA 90:7240–7244, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takeuchi, K., Okabe, S. Mechanism of gastric alkaline response in the stomach after damage roles of nitric oxide and prostaglandins. Digest Dis Sci 40, 865–871 (1995). https://doi.org/10.1007/BF02064993
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02064993