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 Ca2+([Ca2+]i) and inhibited both the outward and inward Na+/Ca2+ 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 [Ca2+]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.
Highlights
Bile acids (BAs), main component of bile, are synthesized from cholesterol in liver microsomes, where they are conjugated with glycine or taurine[1]
bile acids (BAs) can be divided into hydrophobic BAs and hydrophilic BAs, and have a relaxant effect on the smooth muscle in various organs[15,17,18]
The relaxant activity of BAs is related to its hydrophobicity; hydrophobic BAs have a greater potential to relax smooth muscle than hydrophilic BAs19
Summary
Bile acids (BAs), main component of bile, are synthesized from cholesterol in liver microsomes, where they are conjugated with glycine or taurine[1]. BAs, in addition to their classic function in lipid digestion, act as signaling molecules with systemic endocrine functions, such as the regulation of bile acid, glucose and lipid metabolism; the immune response; and cell proliferation and differentiation[2,5]. BAs regulate glucose and lipid homeostasis by activating both the nuclear receptor farnesoid X receptor (FXR) and the plasma membrane-bound G protein-coupled bile acid receptor 5 (TGR5, known as GPBAR1)[7]. DCA can activate TGR5 to relax the gallbladder smooth muscle and intestinal smooth muscle[9]. Considering the important role of BAs in the smooth muscle of gallbladder and intestine, it is necessary to investigate the role of BAs on the bladder, which is a hollow organ composed of smooth muscle and to determine the distribution of BAs. In this study, we investigated the effect of hydrophobic BAs on the detrusor contractility of rat bladder
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