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The effects of hydrogen sulfide on electrical field stimulation-induced neurogenic contractile responses in isolated rabbit lower esophageal sphincter: Contribution of nitrergic and non-adrenergic non-cholinergic transmission

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Abstract

Background

Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits.

Methods

An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer. The nerve-evoked contractile responses were obtained by EFS. The contractile responses were obtained as biphasic “on” and “off” phases seen at the beginning and end of EFS, respectively.

Results

Sodium hydrogen sulfide (NaHS) reduced the EFS-mediated “off” phase and the EFS-mediated non-adrenergic non-cholinergic (NANC) “off” phase. NaHS reduced the EFS-mediated “on” phase as well. l-Cysteine reduced the EFS-mediated “off” phase and the EFS-mediated NANC “off” phase. l-Propargylglycine (PAG) did not affect the EFS-mediated “off” phase or the EFS-mediated NANC “off” phase. NaHS, l-cysteine, and PAG reduced the EFS-mediated, NO-independent “off” phase. The effect of NaHS in all of the experiments returned in time. Also, NaHS caused significant relaxation of 80-mM KCl-Krebs solution induced-contractions, while l-cysteine and PAG did not cause a significant relaxation.

Conclusion

These findings suggest that H2S has an inhibitory effect on the lower esophageal sphincter muscle. While the effect of H2S on EFS-mediated responses disappeared in time, the effect of H2S sustained the KCl-Krebs solution-induced contractions. This shows that H2S may have an effect on neurotransmission at the nerve terminal.

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References

  1. Wang R. Hydrogen sulfide: the third gasotransmitter in biology and medicine. Antioxid Redox Signal 2010;12(9):1061–4.

    Article  CAS  PubMed  Google Scholar 

  2. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 1996;16(3):1066–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Li L, Moore PK. An overview of the biological significance of endogenous gases: new roles for old molecules. Biochem Soc Trans 2007;35(Pt 5):1138–41.

    Article  CAS  PubMed  Google Scholar 

  4. Doeller JE, Isbell TS, Benavides G, Koenitzer J, Patel H, Patel RP, et al. Polarographic measurement of hydrogen sulfide production and consumption by mammalian tissues. Anal Biochem 2005;341(1):40–51.

    Article  CAS  PubMed  Google Scholar 

  5. Stipanuk MH, Beck PW. Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J 1982;206(2):267–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Hosoki R, Matsuki N, Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun 1997;237(3):527–31.

    Article  CAS  PubMed  Google Scholar 

  7. Chen X, Jhee KH, Kruger WD. Production of the neuromodulator H2S by cystathionine—synthase via the condensation of cysteine and homocysteine. J Biol Chem 2004;279(50):52082–6.

    Article  CAS  PubMed  Google Scholar 

  8. Stipanuk MH, De la Rosa J, Hirschberger LL. Catabolism of cysteine by rat renal cortical tubules. J Nutr 1990;120(5):450–8.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J 2001;20(21):6008–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gallego D, Clavé P, Donovan J, Rahmati R, Grundy D, Jiménez M, et al. The gaseous mediator, hydrogen sulphide, inhibits in vitro motor patterns in the human, rat and mouse colon and jejunum. Neurogastroenterol Motil 2008;20:1306–16.

    Article  CAS  PubMed  Google Scholar 

  11. Dhaese I, Lefebvre RA. Myosin light chain phosphatase activation is involved in the hydrogen sulfide-induced relaxation in mouse gastric fundus. Eur J Pharmacol 2009;606:180–6.

    Article  CAS  PubMed  Google Scholar 

  12. Dhaese I, Van Colen I, Lefebvre RA. Mechanisms of action of hydrogen sulfide in relaxation of mouse distal colonic smooth muscle. Eur J Pharmacol 2010;628:179–86.

    Article  CAS  PubMed  Google Scholar 

  13. Nagao M, Linden DR, Duenes JA, Sarr MG. Mechanisms of action of the gasotransmitter hydrogen sulfide in modulating contractile activity of longitudinal muscle of rat ileum. J Gastrointest Surg 2011;15:12–22.

    Article  PubMed  Google Scholar 

  14. Zhang L, Zhao W, Zheng Z, Wang T, Zhao C, Zhou G, et al. Reduction of hydrogen sulfide synthesis enzymes in the esophagus of patients with achalasia: effect of hydrogen sulfide in achalasia. Neurogastroenterol Motil 2015;27(9):1274–81.

    Article  CAS  PubMed  Google Scholar 

  15. Shiina T, Shima T, Horii K, Naitou K, Nakamori H, Sano Y, et al. Inhibitory action of hydrogen sulfide on esophageal striated muscle motility in rats. Eur J Pharmacol 2016;15(771):123–9.

    Article  CAS  Google Scholar 

  16. Schicho R, Krueger D, Zeller F, Von Weyhern CW, Frieling T, Kimura H, et al. Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon. Gastroenterology 2006;131(5):1542–52.

    Article  CAS  PubMed  Google Scholar 

  17. Martin GR, McKnight GW, Dicay MS, Coffin CS, Ferraz JG, Wallace JL. Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract. Dig Liver Dis 2010;42(2):103–9.

    Article  CAS  PubMed  Google Scholar 

  18. Cotton BR, Smith G. The lower oesophageal sphincter and anaesthesia. Br J Anaesth 1984;56:37–46.

    Article  CAS  PubMed  Google Scholar 

  19. Sanders KM, Ward SM. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 1992;262:G379–92.

    CAS  PubMed  Google Scholar 

  20. Tøttrup A, Knudsen MA, Gregersen H. The role of the L-arginine-nitric oxide pathway in relaxation of the opossum lower oesophageal sphincter. Br J Pharmacol 1991;104(1):113–6.

    Article  PubMed  PubMed Central  Google Scholar 

  21. De Man JG, Pelckmans PA, Boeckxstaens GE, Bult H, Oosterbosch L, Herman AG, et al. The role of nitric oxide in inhibitory non-adrenergic non-cholinergic neurotransmission in the canine lower esophageal sphincter. Br J Pharmacol 1991;103(1):1092–6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Uc A, Oh ST, Murray JA, Clark E, Conklin JL. Biphasic relaxation of the opossum lower esophageal sphincter: roles of NO, VIP, and CGRP. Am J Physiol 1999;277(3 Pt 1):548–54.

    Google Scholar 

  23. Farré R, Aulí M, Lecea B, Martínez E, Clavé P. Pharmacologic characterization of intrinsic mechanisms controlling tone and relaxation of porcine lower esophageal sphincter. J Pharmacol Exp Ther 2006;316(3):1238–48.

    Article  PubMed  CAS  Google Scholar 

  24. Farré R, Sifrim D. Regulation of basal tone: relaxation and contraction of the lower oesophageal sphincter: relevance to drug discovery for esophageal disorders. Br J Pharmacol 2008;153(5):858–69.

    Article  PubMed  CAS  Google Scholar 

  25. Cellek S, Moncada S. Nitrergic modulation of cholinergic responses in the opossum lower oesophageal sphincter. Br J Pharmacol 1997;122(6):1043–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lund GF, Christensen J. Electrical stimulation of esophageal smooth muscle and effects of antagonists. Am J Physiol 1969;217(5):1369–74.

    Article  CAS  PubMed  Google Scholar 

  27. Knudsen MA, Svane D, Tøttrup A. Importance of the L-arginine-nitric oxide pathway in NANC nerve function of the opossum esophageal body. Dig Dis 1991;9(6):365–70.

    Article  CAS  PubMed  Google Scholar 

  28. Cheng Y, Ndisang JF, Tang G, Cao K, Wang R. Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol 2004;287(5):2316–23.

    Article  CAS  Google Scholar 

  29. Lowicka E, Betowski J. Hydrogen sulfide (H2S)-the third gas of interest for pharmacologists. Pharmacol Rep 2007;59(1):4–24.

    CAS  PubMed  Google Scholar 

  30. Wang R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J 2002;16(13):1792–8.

    Article  CAS  PubMed  Google Scholar 

  31. Zhao W, Ndisang JF, Wang R. Modulation of endogenous production of H2S in rat tissues. Can J Physiol Pharmacol 2003;81(9):848–53.

    Article  CAS  PubMed  Google Scholar 

  32. Geng B, Cui Y, Zhao J, Yu F, Zhu Y, Xu G, et al. Hydrogen sulfide downregulates the aortic L-arginine/nitric oxide pathway in rats. Am J Physiol Regul Integr Comp Physiol 2007;293(4):1608–18.

    Article  CAS  Google Scholar 

  33. Wang YF, Mainali P, Tang CS, Shi L, Zhang CY, Yan H, et al. Effects of nitric oxide and hydrogen sulfide on the relaxation of pulmonary arteries in rats. Chin Med J (Engl) 2008;121(5):420–3.

    Article  CAS  Google Scholar 

  34. Zhao W, Wang R. H(2)S-induced vasorelaxation and underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol 2002;283(2):474–80.

    Article  Google Scholar 

  35. Ghasemi M, Dehpour AR, Moore KP, Mani AR. Role of endogenous hydrogen sulfide in neurogenic relaxation of rat corpus cavernosum. Biochem Pharmacol 2012;83(9):1261–8.

    Article  CAS  PubMed  Google Scholar 

  36. Teague B, Asiedu S, Moore PK. The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility. Br J Pharmacol 2002;137:139–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Linden DR, Levitt MD, Farrugia G, Szurszewski JH. Endogenous production of H2S in the gastrointestinal tract: still in search of a physiologic function. Antioxid Redox Signal 2010;12(9):1135–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kasparek MS, Linden DR, Farrugia G, Sarr MG. Hydrogen sulfide modulates contractile function in rat jejunum. J Surg Res 2012;175(2):234–42.

    Article  CAS  PubMed  Google Scholar 

  39. Cooper CE, Brown GC. The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance. J Bioenerg Biomembr 2008;40:533–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey

    Halil Kara

  2. Turkish Medicines and Medical Devices Agency, Ministry of Health, Ankara, Turkey

    Fatma Isli

  3. Department of Medical Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Gokce Sevim Ozturk Fincan & Yusuf Sarioglu

  4. Ankara Numune Education and Research Hospital, University of Health Sciences, Ankara, Turkey

    Seniz Yildirim

  5. Turkish Academy of Science, Ankara, Turkey

    Sevim Ercan

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  1. Halil Kara
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  2. Fatma Isli
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Correspondence to Gokce Sevim Ozturk Fincan.

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Kara, H., Isli, F., Ozturk Fincan, G.S. et al. The effects of hydrogen sulfide on electrical field stimulation-induced neurogenic contractile responses in isolated rabbit lower esophageal sphincter: Contribution of nitrergic and non-adrenergic non-cholinergic transmission. Pharmacol. Rep 68, 1350–1357 (2016). https://doi.org/10.1016/j.pharep.2016.09.007

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