Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5.

ABSTRACT: Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists. The bile acid-induced cAMP production does not lead to an increase in contraction rate, and seems to be mediated by the RI isoform of adenylate

SUBMITTER: Ibrahim E 

PROVIDER: S-EPMC5940781 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature