Effect of bile acids on intracellular calcium in isolated rat hepatocyte couplets.
The effects of bile acids on cytosolic free calcium ([Ca2+]i) were studied in single isolated rat hepatocyte couplets using a scanning laser cytometer and the fluorescent dye, indo-1. Cholestatic bile acids, chenodeoxycholate (CDC) and taurolithocholate (TLC) increased [Ca2+]i in a dose-dependent manner. Choleretic bile acids, tauroursodeoxycholate (TUDC) and taurocholate (TC), did not induce any change in [Ca2+]i except TC at very high doses. Treatment with TUDC added concomitantly with CDC or TLC significantly decreased the rise in [Ca2+]i induced by bile acids. These results, obtained with a polarized hepatocyte model that secretes bile, confirmed that cholestatic bile acids increase [Ca2+]i and showed that TUDC inhibits this phenomenon. These data are in agreement with a key role of intracellular calcium in cholestasis.
Thibault
N
N
Drug Safety Department, Rhône-Poulenc Rorer S.A. BP 14, Vitry sur Seine, France.
Ballet
F
F
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013658:Taurolithocholic Acid / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D014667:Vasopressins; D013655:Taurochenodeoxycholic Acid; D013658:Taurolithocholic Acid; C031655:ursodoxicoltaurine; D002118:Calcium