title: Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na⁺/Ca²⁺ exchanger.
abstract: 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 (INCX) 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.
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Xingyou
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Longkun
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D042541:Intracellular Space / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D008095:Lithocholic Acid / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
chemical_list: D001647:Bile Acids and Salts; C518268:Gpbar1 protein, rat; D043562:Receptors, G-Protein-Coupled; D019831:Sodium-Calcium Exchanger; D008095:Lithocholic Acid; D002118:Calcium