Neuronal NO synthase blocker 7-nitroindazole suppressed bicarbonate secretion in rat gastric mucosa induced by mild local irritation with 1 M NaCl (pH 2.0). Non-selective blocker of neuronal and endothelial synthases, Nω-nitro-L-arginine (L-NNA), did not affect HCO3– production, but inhibited secretion after pretreatment with omeprazole. Non-selective cyclooxygenase blocker indomethacin inhibited HCO3– production under conditions of normal synthase activity and in the presence of L-NNA, but was ineffective when co-administered with 7-nitroindazole. It was concluded that neuronal and endothelial synthases are involved in different mechanisms of regulation of HCO3– secretion in the gastric mucosa induced by mild irritation. Activation of neuronal synthase stimulated HCO3– production, which is mediated mainly through activation of cyclooxygenase. Theoretically, activation of endothelial synthase should suppress HCO3– production. The effect of endothelial synthase depends on acid secretion in the stomach and bicarbonate concentration in the submucosa, as it was demonstrated in experiments with intravenous NaHCO3 infusion.
Zolotarev VA, Andreeva YuV, Vershinina EA, Kropycheva RP. Roles of constitutive synthases of nitric oxide in the regulation of gastric bicarbonate secretion induced by mild irritation of the mucosa. Ross. Fiziol. Zh. 2015;101(4):415-432. Russian.Google Scholar
Zolotarev VA, Polenov SA, Lepnev GP, Razumova NA. A method of continuous recording of acid and bicarbonate secretion in the stomach of anesthetized rats. Ross. Fiziol. Zh. 1996;82(7):111-116. Russian.Google Scholar
Aihara E, Kagawa S, Hayashi M, Takeuchi K. ACE inhibitor and AT1 antagonist stimulate duodenal HCO3— secretion mediated by a common pathway — involvement of PG, NO and bradykinin. J. Physiol. Pharmacol. 2005;56(3):391-406.PubMedGoogle Scholar
Aihara E, Sasaki Y, Ise F, Kita K, Nomura Y, Takeuchi K. Distinct mechanisms of acid-induced HCO3— secretion in normal and slightly permeable stomachs. Am. J. Physiol. Gastrointest. Liver Physiol. 2006;291(3):G464-G471.CrossRefPubMedGoogle Scholar
Bush MA, Pollack GM. Pharmacokinetics and pharmacodynamics of 7-nitroindazole, a selective nitric oxide synthase inhibitor, in the rat hippocampus. Pharm. Res. 2001;18(11):1607-1612.CrossRefPubMedGoogle Scholar
Cuzzocrea S, Salvemini D. Molecular mechanisms involved in the reciprocal regulation of cyclooxygenase and nitric oxide synthase enzymes. Kidney Int. 2007;71(4):290-297.CrossRefPubMedGoogle Scholar
Lamarque D, Dutreuil C, Dhumeaux D, Delchier JC. Increased gastric bicarbonate secretion in portal hypertensive anesthetized rats: role of prostaglandins and nitric oxide. Dig. Dis. Sci. 1997;42(4):743-750.CrossRefPubMedGoogle Scholar
Phillipson M, Atuma C, Henriksnäs J, Holm L. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH. Am. J. Physiol. Gastrointest. Liver Physiol. 2002;282(2):G211-G219.CrossRefPubMedGoogle Scholar
Phillipson M, Henriksnäs J, Holstad M, Sandler S, Holm L. Inducible nitric oxide synthase is involved in acid-induced gastric hyperemia in rats and mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2003;285(1):G154-G162.CrossRefPubMedGoogle Scholar
Price KJ, Hanson PJ, Whittle BJ. Localization of constitutive isoforms of nitric oxide synthase in the gastric glandular mucosa of the rat. Cell Tissue Res. 1996;285(1):157-163.CrossRefPubMedGoogle Scholar
Southan GJ, Szabó C. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem. Pharmacol. 1996;51(4):383-394.CrossRefPubMedGoogle Scholar
Takeuchi K. Gastric cytoprotection by prostaglandin E2 and prostacyclin: relationship to EP1 and IP receptors. J. Physiol. Pharmacol. 2014;65(1):3-14.PubMedGoogle Scholar
Takeuchi K, Aihara E, Sasaki Y, Nomura Y, Ise F. Involvement of cyclooxygenase-1, prostaglandin E2 and EP1 receptors in acid-induced HCO3— secretion in stomach. J. Physiol. Pharmacol. 2006;57(4):661-676.PubMedGoogle Scholar
Tanaka A, Kunikata T, Mizoguchi H, Kato S, Takeuchi K. Dual action of nitric oxide in pathogenesis of indomethacininduced small intestinal ulceration in rats. J. Physiol. Pharmacol. 1999;50(3):405-417.PubMedGoogle Scholar
Víteček J, Lojek A, Valacchi G, Kubala L. Arginine-based inhibitors of nitric oxide synthase: therapeutic potential and challenges. Mediators Inflamm. 2012;2012. ID 318087. doi: 10.1155/2012/318087.