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Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger

Hydrophobic bile acids (BAs) are thought to inhibit smooth muscle contractility in several organs. The present study was undertaken to investigate the effects of hydrophobic BAs on the detrusor contractility of rat bladder and to explore the possible mechanism. Lithocholic acid (LCA) treatment incre...

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Autores principales: Zhu, Jingzhen, Dong, Xingyou, Liu, Qian, Wu, Chao, Wang, Qingqing, Long, Zhou, Li, Longkun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759538/
https://www.ncbi.nlm.nih.gov/pubmed/26892434
http://dx.doi.org/10.1038/srep21358
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author Zhu, Jingzhen
Dong, Xingyou
Liu, Qian
Wu, Chao
Wang, Qingqing
Long, Zhou
Li, Longkun
author_facet Zhu, Jingzhen
Dong, Xingyou
Liu, Qian
Wu, Chao
Wang, Qingqing
Long, Zhou
Li, Longkun
author_sort Zhu, Jingzhen
collection PubMed
description Hydrophobic bile acids (BAs) are thought to inhibit smooth muscle contractility in several organs. The present study was undertaken to investigate the effects of hydrophobic BAs on the detrusor contractility of rat bladder and to explore the possible mechanism. Lithocholic acid (LCA) treatment increased the micturition interval and induced a concentration-dependent relaxation of bladder detrusor strips. In addition, LCA reduced the concentration of intracellular free Ca(2+)([Ca(2+)](i)) and inhibited both the outward and inward Na(+)/Ca(2+) exchanger (NCX) current (I(NCX)) in primary isolated smooth muscle cells (SMCs). To further investigate the mechanism of action of LCA, several pharmacologic agents were used. We found that the NCX inhibitor 3′,4′-Dichlorobenzamil (DCB) can significantly inhibit the relaxation of detrusor strips and a reduction of the [Ca(2+)](i) induced by LCA, while the antagonist of muscarinic receptor and the agonist of the G protein-coupled bile acid receptor (TGR5) and the farnesoid X receptor (FXR) had no effect. In conclusion, these data suggest that the relaxation of rat detrusor induced by hydrophobic BAs is mediated by NCX. Further research is needed to carry out to demonstrate the possible pathway and provide a potential new strategy to investigation for the treatment of the low urinary tract syndromes.
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spelling pubmed-47595382016-02-26 Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger Zhu, Jingzhen Dong, Xingyou Liu, Qian Wu, Chao Wang, Qingqing Long, Zhou Li, Longkun Sci Rep Article Hydrophobic bile acids (BAs) are thought to inhibit smooth muscle contractility in several organs. The present study was undertaken to investigate the effects of hydrophobic BAs on the detrusor contractility of rat bladder and to explore the possible mechanism. Lithocholic acid (LCA) treatment increased the micturition interval and induced a concentration-dependent relaxation of bladder detrusor strips. In addition, LCA reduced the concentration of intracellular free Ca(2+)([Ca(2+)](i)) and inhibited both the outward and inward Na(+)/Ca(2+) exchanger (NCX) current (I(NCX)) in primary isolated smooth muscle cells (SMCs). To further investigate the mechanism of action of LCA, several pharmacologic agents were used. We found that the NCX inhibitor 3′,4′-Dichlorobenzamil (DCB) can significantly inhibit the relaxation of detrusor strips and a reduction of the [Ca(2+)](i) induced by LCA, while the antagonist of muscarinic receptor and the agonist of the G protein-coupled bile acid receptor (TGR5) and the farnesoid X receptor (FXR) had no effect. In conclusion, these data suggest that the relaxation of rat detrusor induced by hydrophobic BAs is mediated by NCX. Further research is needed to carry out to demonstrate the possible pathway and provide a potential new strategy to investigation for the treatment of the low urinary tract syndromes. Nature Publishing Group 2016-02-19 /pmc/articles/PMC4759538/ /pubmed/26892434 http://dx.doi.org/10.1038/srep21358 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhu, Jingzhen
Dong, Xingyou
Liu, Qian
Wu, Chao
Wang, Qingqing
Long, Zhou
Li, Longkun
Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger
title Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger
title_full Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger
title_fullStr Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger
title_full_unstemmed Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger
title_short Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na(+)/Ca(2+) exchanger
title_sort hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the na(+)/ca(2+) exchanger
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759538/
https://www.ncbi.nlm.nih.gov/pubmed/26892434
http://dx.doi.org/10.1038/srep21358
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