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Mechanisms of Action of the Gasotransmitter Hydrogen Sulfide in Modulating Contractile Activity of Longitudinal Muscle of Rat Ileum

  • 2010 SSAT Poster Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Aim

This study aims to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H2S) on contractile activity in longitudinal muscle of rat ileum.

Methods

Ileal longitudinal muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a donor of H2S, were evaluated on spontaneous contractile activity and after enhanced contractile activity with bethanechol. l-cysteine was evaluated as a potential endogenous donor of H2S. We evaluated involvement of extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, and K +ATP channel and K +Ca channel activity on the action of H2S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, l-NG-nitro arginine (l-NNA), glibenclamide, and apamin, respectively, as well as electrical field stimulation.

Result

NaHS dose-dependently and reversibly inhibited spontaneous and bethanechol-stimulated contractile activity (p < 0.05). l-cysteine had no inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, l-NNA, glibenclamide, or apamin had no major effect on total contractile activity by NaHS, although both tetrodotoxin and apamin decreased the frequency of bethanechol-enhanced contractile activity (p < 0.05). We could not demonstrate H2S release by electrical field stimulation but did show that inhibition of cystathionine β synthase, an endogenous source of H2S, augmented the inhibitory effect of low-frequency electrical field stimulation.

Conclusion

H2S inhibits contractile activity of ileal longitudinal muscle dose-dependently but not through pathways mediated by the extrinsic or enteric nervous system, visceral afferent nerves, nitric oxide, K +ATP channels, or K +Ca channels.

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References

  1. Wang R. The gasotransmitter role of hydrogen sulfide. Antioxid Redox Signal. 2003;5:493–501.

    Article  PubMed  Google Scholar 

  2. Kasparek MS, Linden DR, Kreis ME, Sarr MG. Gasotransmitters in the gastrointestinal tract. Surgery 2008;143:455–459.

    Article  PubMed  Google Scholar 

  3. Lowicka E, Beltowski J. Hydrogen sulfide (H2S)-the third gas of interest for pharmacolgists. Pharmacol Rep 2007;59:4–24.

    PubMed  CAS  Google Scholar 

  4. Gallego D, Clave P, Donovan J, Rahmati R, Grundy D, Jimenez M, Beyak MJ. The gaseous mediator, hydrogen sulphide, inhibits in vitro motor patterns in the human, rat and mouse colon and jejunum. Neurogatroenterol Motil 2008;20:1306–1316.

    Article  CAS  Google Scholar 

  5. Teague B, Asiedu S, Moore PK. The smooth muscle relaxant effect of hydrogen sulfide in vitro: evidence for a physiological role to control intestinal contractility. Br J Pharmachol 2002;137:139–145.

    Article  CAS  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;237:527–531.

    Article  PubMed  CAS  Google Scholar 

  7. Kasparek MS, Fatima J, Iqbal CW, Duenes JA, Sarr MG. Age-related changes in functional NANC innervation with VIP and substance P in the jejunum of Lewis rats. Auton Neurosci. 2009;151:127–134.

    Article  PubMed  CAS  Google Scholar 

  8. Kasparek MS, Fatima J, Iqbal CW, Duenes JA, Sarr MG. Role of VIP and substance P in NANC innervation in the longitudinal smooth muscle of the rat jejunum—influence of extrinsic denervation. J Surg Res. 2007;141:22–30.

    Article  PubMed  CAS  Google Scholar 

  9. Dombkowski RA, Russell MJ, Olson KR. Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout. Am J Physiol Regul Integr Comp Physiol. 2004;286:678–685.

    Article  Google Scholar 

  10. Ohtani N, Balsiger BM, Anding WJ, Duenes JA, Sarr MG. Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats. J Gastrointestinal Surg 2000;4:77–85.

    Article  CAS  Google Scholar 

  11. Schicho R, Krueger D, Zeller F, Von Weyhern CW, Frieling T, Kimura H, Ishii I, De Giorgio R, Campi B, Schemann M. Hydrogen sulfide is a novel prosecretory neuromodulator in the guinea-pig and human colon. Gastroenterology 2006;131:1542–1552.

    Article  PubMed  CAS  Google Scholar 

  12. Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. pharmacol Rev 1991;43:143–201.

    PubMed  CAS  Google Scholar 

  13. Holzer P. Capsaicin as a tool for studying sensory neuron functions. Adv Exp Med Biol 1991;298:3–16.

    PubMed  CAS  Google Scholar 

  14. Patacchini R, Santicioli P, Giuliani S, Maggi CA. Hydrogen sulfide (H2S) stimulated capsaicin-sensitive primary afferent neurons in the rat urinary bladder. Br J Pharmachol 2004;142:31–34.

    Article  CAS  Google Scholar 

  15. Trevisani M, Patacchini R, Nicoletti P, Gatti R, Gazzieri D, Lissi N, Zagli G, Creminon C, Geppetti P, Harrison S. Hydrogen sulfide causes vanilloid receptor 1-mediated neurogenic inflammation in the airways. Br J Pharmachol 2005;145:1123–1131.

    Article  CAS  Google Scholar 

  16. Linden DR, Sha L, Mazzone A, Stoltz GJ, Bernard CE, Furne JK, Farrugia G, Szurszewski JH. Production of the gaseous signal molecule hydrogen sulfide in mouse tissues. J neurochem 2008;106:1577–1585.

    PubMed  CAS  Google Scholar 

  17. Kasparek MS, Fatima J, Iqbal CW, Duenes JA, Sarr MG. Long-Term Effects of Extrinsic Denervation on VIP and Substance P Innervation in Circular Muscle of Rat Jejunum. J Gastrointestinal Surg 2007;11:1339–1350.

    Article  Google Scholar 

  18. Kasparek MS, Fatima J, Iqbal CW, Duenes JA, Sarr MG. Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum. Neurogatroenterol Motil 2008;20:243–252.

    Article  CAS  Google Scholar 

  19. Kasparek MS, Fatima J, Iqbal CW, Sarr MG. Effects of extrinsic denervation on innervation with VIP and substance P in circular muscle of rat jejunum. Neurogatroenterol Motil 2008;20:808–817.

    Article  CAS  Google Scholar 

  20. Linden DR, Levitt MD, Farrugia G, Szurszewski JH. Endogenous production of H2S in the gastrointestinal tract: still in search of a physiologic function. Antioxidants & redox signaling 2010;12:1135–1146.

    Article  PubMed  CAS  Google Scholar 

  21. Ali MY, Ping CY, Mok YY, Ling L, Whiteman M, Bhatia M, Moore P. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulfide? Br J Pharmachol 2006;149:625–634.

    Article  CAS  Google Scholar 

  22. Fiorucci S, Distrutti E, Cirino G, Wallace JL. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology 2006;131:259–271.

    Article  PubMed  CAS  Google Scholar 

  23. Wang R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J 2002;16:1792–1798.

    Article  PubMed  CAS  Google Scholar 

  24. Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Antonelli E, Roviezzo F, Morelli A, Cirino G, Wallace JL, Fiorucci S. Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels. J Pharmacol Exp Ther 2006;316:325–335.

    Article  PubMed  CAS  Google Scholar 

  25. Dhaese I, Van Colen I, Lefebvre RA. Mechanisms of action of hydrogen sulfide in relaxation of mouse distal colonic smooth muscle. Eur J Pharmacol 2009;628:179–186.

    Article  PubMed  Google Scholar 

  26. Mustafa AK, Gadalla MM, Snyder SH. Signaling by gasotransmitters. Sci Signal 2009;2.

  27. Gadalla MM, Snyder SH. Hydrogen sulfide as a gasotransmitter. J neurochem 2010;113:14–26.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors want to thank Deborah I. Frank for her assistance in the preparation of this manuscript, Julie K. Furne, Gary J. Stoltz, and Lei Sha for their technical assistance.

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Authors and Affiliations

  1. Gastroenterology Research Unit and Division of Gastroenterologic and General Surgery, Rochester, MN, 55905, USA

    Munenori Nagao, Judith A. Duenes & Michael G. Sarr

  2. Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    David R. Linden

  3. Gastroenterology Research Unit (Guggenheim 10-01), Mayo Clinic, 200 First Ave SW, Rochester, MN, 55905, USA

    Michael G. Sarr

Authors
  1. Munenori Nagao
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  2. David R. Linden
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  3. Judith A. Duenes
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  4. Michael G. Sarr
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Corresponding author

Correspondence to Michael G. Sarr.

Additional information

This work was supported in part by a grant from the National Institutes of Health, DK39337-19 (MGS).

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Nagao, M., Linden, D.R., Duenes, J.A. et al. Mechanisms of Action of the Gasotransmitter Hydrogen Sulfide in Modulating Contractile Activity of Longitudinal Muscle of Rat Ileum. J Gastrointest Surg 15, 12–22 (2011). https://doi.org/10.1007/s11605-010-1306-8

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  • DOI: https://doi.org/10.1007/s11605-010-1306-8

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