Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger
Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Chang...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2018-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X17301595 |
| _version_ | 1819163811531194368 |
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| author | Xiaopeng Bai Eikichi Ihara Katsuya Hirano Yoshimasa Tanaka Kayoko Nakano Satomi Kita Takahiro Iwamoto Haruei Ogino Mayumi Hirano Yoshinao Oda Kazuhiko Nakamura Yoshihiro Ogawa |
| author_facet | Xiaopeng Bai Eikichi Ihara Katsuya Hirano Yoshimasa Tanaka Kayoko Nakano Satomi Kita Takahiro Iwamoto Haruei Ogino Mayumi Hirano Yoshinao Oda Kazuhiko Nakamura Yoshihiro Ogawa |
| author_sort | Xiaopeng Bai |
| collection | DOAJ |
| description | Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question.
Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function.
Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice.
Conclusions: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia. |
| first_indexed | 2024-12-22T17:50:04Z |
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| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-22T17:50:04Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
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| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-0d402d4e1a4b4f49905c41cbab2ae8e82022-12-21T18:18:11ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2018-01-015320922110.1016/j.jcmgh.2017.11.004Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ ExchangerXiaopeng Bai0Eikichi Ihara1Katsuya Hirano2Yoshimasa Tanaka3Kayoko Nakano4Satomi Kita5Takahiro Iwamoto6Haruei Ogino7Mayumi Hirano8Yoshinao Oda9Kazuhiko Nakamura10Yoshihiro Ogawa11Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa Prefecture, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDivision of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanHydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. Conclusions: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia.http://www.sciencedirect.com/science/article/pii/S2352345X17301595Lower Esophageal SphincterMyogenic Tone RegulationHydrogen SulfateNa+/Ca2+ Exchanger |
| spellingShingle | Xiaopeng Bai Eikichi Ihara Katsuya Hirano Yoshimasa Tanaka Kayoko Nakano Satomi Kita Takahiro Iwamoto Haruei Ogino Mayumi Hirano Yoshinao Oda Kazuhiko Nakamura Yoshihiro Ogawa Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger Cellular and Molecular Gastroenterology and Hepatology Lower Esophageal Sphincter Myogenic Tone Regulation Hydrogen Sulfate Na+/Ca2+ Exchanger |
| title | Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger |
| title_full | Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger |
| title_fullStr | Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger |
| title_full_unstemmed | Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger |
| title_short | Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger |
| title_sort | endogenous hydrogen sulfide contributes to tone generation in porcine lower esophageal sphincter via na ca2 exchanger |
| topic | Lower Esophageal Sphincter Myogenic Tone Regulation Hydrogen Sulfate Na+/Ca2+ Exchanger |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X17301595 |
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