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Published in: BMC Gastroenterology 1/2004

Open Access 01-12-2004 | Research article

Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands

Authors: Anna Berg, Stefan Redeen, Ann-Charlott Ericson, Sven Erik Sjöstrand

Published in: BMC Gastroenterology | Issue 1/2004

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Abstract

Background

Endothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.

Methods

Oxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [14C]aminopyrine.

Results

The histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA) enhanced the secretory response.

Conclusion

Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.
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Literature
2.
go back to reference Palacios M, Knowles RG, Palmer RM, Moncada S: Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochemical & Biophysical Research Communications. 1989, 165: 802-9.CrossRef Palacios M, Knowles RG, Palmer RM, Moncada S: Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochemical & Biophysical Research Communications. 1989, 165: 802-9.CrossRef
3.
go back to reference Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980, 288: 373-6.CrossRefPubMed Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980, 288: 373-6.CrossRefPubMed
4.
go back to reference Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G: Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proceedings of the National Academy of Sciences of the United States of America. 1987, 84: 9265-9.CrossRefPubMedPubMedCentral Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G: Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proceedings of the National Academy of Sciences of the United States of America. 1987, 84: 9265-9.CrossRefPubMedPubMedCentral
5.
go back to reference Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological Reviews. 1991, 43: 109-42.PubMed Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological Reviews. 1991, 43: 109-42.PubMed
6.
go back to reference Calatayud S, Sanz MJ, Canet A, Bello R, de Rojas FD, Esplugues JV: Mechanisms of gastroprotection by transdermal nitroglycerin in the rat. British Journal of Pharmacology. 1999, 127: 1111-8.CrossRefPubMedPubMedCentral Calatayud S, Sanz MJ, Canet A, Bello R, de Rojas FD, Esplugues JV: Mechanisms of gastroprotection by transdermal nitroglycerin in the rat. British Journal of Pharmacology. 1999, 127: 1111-8.CrossRefPubMedPubMedCentral
7.
go back to reference Wallace JL, Granger DN: The cellular and molecular basis of gastric mucosal defense. FASEB Journal. 1996, 10: 731-40.PubMed Wallace JL, Granger DN: The cellular and molecular basis of gastric mucosal defense. FASEB Journal. 1996, 10: 731-40.PubMed
8.
go back to reference Brown JF, Hanson PJ, Whittle BJ: Nitric oxide donors increase mucus gel thickness in rat stomach. European Journal of Pharmacology. 1992, 223: 103-4. 10.1016/0014-2999(92)90824-N.CrossRefPubMed Brown JF, Hanson PJ, Whittle BJ: Nitric oxide donors increase mucus gel thickness in rat stomach. European Journal of Pharmacology. 1992, 223: 103-4. 10.1016/0014-2999(92)90824-N.CrossRefPubMed
9.
go back to reference Takeuchi K, Ohuchi T, Miyake H, Niki S, Okabe S: Effects of nitric oxide synthase inhibitors on duodenal alkaline secretion in anesthetized rats. European Journal of Pharmacology. 1993, 231: 135-8. 10.1016/0014-2999(93)90694-D.CrossRefPubMed Takeuchi K, Ohuchi T, Miyake H, Niki S, Okabe S: Effects of nitric oxide synthase inhibitors on duodenal alkaline secretion in anesthetized rats. European Journal of Pharmacology. 1993, 231: 135-8. 10.1016/0014-2999(93)90694-D.CrossRefPubMed
10.
go back to reference Sababi M, Nilsson E, Holm L: Mucus and alkali secretion in the rat duodenum: effects of indomethacin, N omega-nitro-L-arginine, and luminal acid. Gastroenterology. 1995, 109: 1526-34.CrossRefPubMed Sababi M, Nilsson E, Holm L: Mucus and alkali secretion in the rat duodenum: effects of indomethacin, N omega-nitro-L-arginine, and luminal acid. Gastroenterology. 1995, 109: 1526-34.CrossRefPubMed
11.
go back to reference Holm M, Johansson B, Pettersson A, Fandriks L: Acid-induced duodenal mucosal nitric oxide output parallels bicarbonate secretion in the anaesthetized pig. Acta Physiologica Scandinavica. 1998, 162: 461-8. 10.1046/j.1365-201X.1998.0307f.x.CrossRefPubMed Holm M, Johansson B, Pettersson A, Fandriks L: Acid-induced duodenal mucosal nitric oxide output parallels bicarbonate secretion in the anaesthetized pig. Acta Physiologica Scandinavica. 1998, 162: 461-8. 10.1046/j.1365-201X.1998.0307f.x.CrossRefPubMed
12.
go back to reference Bilski J, Konturek PC, Konturek SJ, Cieszkowski M, Czarnobilski K: Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow and gastrin release in conscious dogs. Regulatory Peptides. 1994, 53: 175-84. 10.1016/0167-0115(94)90166-X.CrossRefPubMed Bilski J, Konturek PC, Konturek SJ, Cieszkowski M, Czarnobilski K: Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow and gastrin release in conscious dogs. Regulatory Peptides. 1994, 53: 175-84. 10.1016/0167-0115(94)90166-X.CrossRefPubMed
13.
go back to reference Brown JF, Hanson PJ, Whittle BJ: The nitric oxide donor, S-nitroso-N-acetyl-penicillamine, inhibits secretory activity in rat isolated parietal cells. Biochemical & Biophysical Research Communications. 1993, 195: 1354-9. 10.1006/bbrc.1993.2192.CrossRef Brown JF, Hanson PJ, Whittle BJ: The nitric oxide donor, S-nitroso-N-acetyl-penicillamine, inhibits secretory activity in rat isolated parietal cells. Biochemical & Biophysical Research Communications. 1993, 195: 1354-9. 10.1006/bbrc.1993.2192.CrossRef
14.
go back to reference Kato S, Kitamura M, Korolkiewicz RP, Takeuchi K: Role of nitric oxide in regulation of gastric acid secretion in rats: effects of NO donors and NO synthase inhibitor. British Journal of Pharmacology. 1998, 123: 839-46.CrossRefPubMedPubMedCentral Kato S, Kitamura M, Korolkiewicz RP, Takeuchi K: Role of nitric oxide in regulation of gastric acid secretion in rats: effects of NO donors and NO synthase inhibitor. British Journal of Pharmacology. 1998, 123: 839-46.CrossRefPubMedPubMedCentral
15.
go back to reference Kim H, Kim KH: Effects of a nitric oxide donor and nitric oxide synthase inhibitors on acid secretion of isolated rabbit gastric glands. Pharmacology. 1996, 53: 331-9.CrossRefPubMed Kim H, Kim KH: Effects of a nitric oxide donor and nitric oxide synthase inhibitors on acid secretion of isolated rabbit gastric glands. Pharmacology. 1996, 53: 331-9.CrossRefPubMed
16.
go back to reference Molero M, Hernandez IM, Lobo P, Cardenas P, Romero R, Chacin J: Modulation by nitric oxide of gastric acid secretion in toads. Acta Physiologica Scandinavica. 1998, 164: 229-36. 10.1046/j.1365-201X.1998.00413.x.CrossRefPubMed Molero M, Hernandez IM, Lobo P, Cardenas P, Romero R, Chacin J: Modulation by nitric oxide of gastric acid secretion in toads. Acta Physiologica Scandinavica. 1998, 164: 229-36. 10.1046/j.1365-201X.1998.00413.x.CrossRefPubMed
17.
go back to reference Hasebe K, Horie S, Yano S, Watanabe K: Inhibitory effect of N(omega)-nitro-L-arginine on gastric secretion induced by secretagogues and vagal stimulation in the isolated stomach. European Journal of Pharmacology. 1998, 350: 229-36. 10.1016/S0014-2999(98)00248-9.CrossRefPubMed Hasebe K, Horie S, Yano S, Watanabe K: Inhibitory effect of N(omega)-nitro-L-arginine on gastric secretion induced by secretagogues and vagal stimulation in the isolated stomach. European Journal of Pharmacology. 1998, 350: 229-36. 10.1016/S0014-2999(98)00248-9.CrossRefPubMed
18.
go back to reference Hasebe K, Horie S, Komasaka M, Yano S, Watanabe K: Stimulatory effects of nitric oxide donors on gastric acid secretion in isolated mouse stomach. Eur J Pharmacol. 2001, 420: 159-64. 10.1016/S0014-2999(01)00995-5.CrossRefPubMed Hasebe K, Horie S, Komasaka M, Yano S, Watanabe K: Stimulatory effects of nitric oxide donors on gastric acid secretion in isolated mouse stomach. Eur J Pharmacol. 2001, 420: 159-64. 10.1016/S0014-2999(01)00995-5.CrossRefPubMed
19.
go back to reference Kawauchi S, Sugamoto S, Furukawa O, Mimaki H, Takeuchi K: Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro. J Physiol Pharmacol. 2001, 52: 93-105.PubMed Kawauchi S, Sugamoto S, Furukawa O, Mimaki H, Takeuchi K: Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro. J Physiol Pharmacol. 2001, 52: 93-105.PubMed
20.
go back to reference Hirsch DP, Tiel-Van Buul MM, Tytgat GN, Boeckxstaens GE: Effect of L-NMMA on postprandial transient lower esophageal sphincter relaxations in healthy volunteers. Dig Dis Sci. 2000, 45: 2069-75. 10.1023/A:1005611221617.CrossRefPubMed Hirsch DP, Tiel-Van Buul MM, Tytgat GN, Boeckxstaens GE: Effect of L-NMMA on postprandial transient lower esophageal sphincter relaxations in healthy volunteers. Dig Dis Sci. 2000, 45: 2069-75. 10.1023/A:1005611221617.CrossRefPubMed
21.
go back to reference Konturek JW, Fischer H, Gromotka PM, Konturek SJ, Domschke W: Endogenous nitric oxide in the regulation of gastric secretory and motor activity in humans. Alimentary Pharmacology & Therapeutics. 1999, 13: 1683-91. 10.1046/j.1365-2036.1999.00598.x.CrossRef Konturek JW, Fischer H, Gromotka PM, Konturek SJ, Domschke W: Endogenous nitric oxide in the regulation of gastric secretory and motor activity in humans. Alimentary Pharmacology & Therapeutics. 1999, 13: 1683-91. 10.1046/j.1365-2036.1999.00598.x.CrossRef
22.
go back to reference Berg A, Kechagias S, Sjostrand SE, Ericson AC: Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans. Scand J Gastroenterol. 2001, 36: 1016-21. 10.1080/003655201750422594.CrossRefPubMed Berg A, Kechagias S, Sjostrand SE, Ericson AC: Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans. Scand J Gastroenterol. 2001, 36: 1016-21. 10.1080/003655201750422594.CrossRefPubMed
23.
go back to reference Berglindh T, Obrink KJ: A method for preparing isolated glands from the rabbit gastric mucosa. Acta Physiol Scand. 1976, 96: 150-9.CrossRefPubMed Berglindh T, Obrink KJ: A method for preparing isolated glands from the rabbit gastric mucosa. Acta Physiol Scand. 1976, 96: 150-9.CrossRefPubMed
24.
go back to reference Fellenius E, Elander B, Wallmark B, Haglund U, Helander HF, Olbe L: A micro-method for the study of acid secretory function in isolated human oxyntic glands from gastroscopic biopsies. Clin Sci (Lond). 1983, 64: 423-31.CrossRef Fellenius E, Elander B, Wallmark B, Haglund U, Helander HF, Olbe L: A micro-method for the study of acid secretory function in isolated human oxyntic glands from gastroscopic biopsies. Clin Sci (Lond). 1983, 64: 423-31.CrossRef
25.
go back to reference Haglund U, Elander B, Fellenius E, Leth R, Rehnberg O, Olbe L: The effects of secretagogues of isolated human gastric glands. Scand J Gastroenterol. 1982, 17: 455-60.CrossRefPubMed Haglund U, Elander B, Fellenius E, Leth R, Rehnberg O, Olbe L: The effects of secretagogues of isolated human gastric glands. Scand J Gastroenterol. 1982, 17: 455-60.CrossRefPubMed
26.
go back to reference Butler AR, Glidewell C, McGinnis J, Bisset WI: Further investigations regarding the toxicity of sodium nitroprusside. Clin Chem. 1987, 33: 490-2.PubMed Butler AR, Glidewell C, McGinnis J, Bisset WI: Further investigations regarding the toxicity of sodium nitroprusside. Clin Chem. 1987, 33: 490-2.PubMed
27.
go back to reference Clancy R, Leszczynska J, Amin A, Levartovsky D, Abramson SB: Nitric oxide stimulates ADP ribosylation of actin in association with the inhibition of actin polymerization in human neutrophils. Journal of Leukocyte Biology. 1995, 58: 196-202.PubMed Clancy R, Leszczynska J, Amin A, Levartovsky D, Abramson SB: Nitric oxide stimulates ADP ribosylation of actin in association with the inhibition of actin polymerization in human neutrophils. Journal of Leukocyte Biology. 1995, 58: 196-202.PubMed
28.
go back to reference Forte TM, Machen TE, Forte JG: Ultrastructural changes in oxyntic cells associated with secretory function: a membrane-recycling hypothesis. Gastroenterology. 1977, 73: 941-55.PubMed Forte TM, Machen TE, Forte JG: Ultrastructural changes in oxyntic cells associated with secretory function: a membrane-recycling hypothesis. Gastroenterology. 1977, 73: 941-55.PubMed
29.
go back to reference McDonald LJ, Murad F: Nitric oxide and cGMP signaling. Advances in Pharmacology (New York). 1995, 34: 263-75.CrossRef McDonald LJ, Murad F: Nitric oxide and cGMP signaling. Advances in Pharmacology (New York). 1995, 34: 263-75.CrossRef
30.
go back to reference Hanafy KA, Krumenacker JS, Murad F: NO, nitrotyrosine, and cyclic GMP in signal transduction. Med Sci Monit. 2001, 7: 801-19.PubMed Hanafy KA, Krumenacker JS, Murad F: NO, nitrotyrosine, and cyclic GMP in signal transduction. Med Sci Monit. 2001, 7: 801-19.PubMed
31.
go back to reference Chen D, Marvik R, Ronning K, Andersson K, Waldum HL, Hakanson R: Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and alpha-fluoromethylhistidine. Regulatory Peptides. 1996, 65: 133-138.CrossRefPubMed Chen D, Marvik R, Ronning K, Andersson K, Waldum HL, Hakanson R: Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and alpha-fluoromethylhistidine. Regulatory Peptides. 1996, 65: 133-138.CrossRefPubMed
32.
go back to reference Salvemini D, Masini E, Pistelli A, Mannaioni PF, Vane J: Nitric oxide: a regulatory mediator of mast cell reactivity. Journal of Cardiovascular Pharmacology. 1991, 17: S258-S264.CrossRef Salvemini D, Masini E, Pistelli A, Mannaioni PF, Vane J: Nitric oxide: a regulatory mediator of mast cell reactivity. Journal of Cardiovascular Pharmacology. 1991, 17: S258-S264.CrossRef
33.
go back to reference Peh KH, Moulson A, Wan BY, Assem EK, Pearce FL: Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells. European Journal of Pharmacology. 2001, 425: 229-238. 10.1016/S0014-2999(01)01205-5.CrossRefPubMed Peh KH, Moulson A, Wan BY, Assem EK, Pearce FL: Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells. European Journal of Pharmacology. 2001, 425: 229-238. 10.1016/S0014-2999(01)01205-5.CrossRefPubMed
Metadata
Title
Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands
Authors
Anna Berg
Stefan Redeen
Ann-Charlott Ericson
Sven Erik Sjöstrand
Publication date
01-12-2004
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2004
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-4-16

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