Effect of bile acids on biliary excretion of cyclosporin A in the rat.
Cyclosporin A, a substrate of P-glycoprotein (P-gp), is known to cause cholestasis in humans and in rat experimental models. Tauroursodeoxycholate is reported to be effective in CyA-induced cholestasis in rats. In the present study, to investigate the mechanism of the inhibition of CyA induced cholestasis, effect of bile acids on biliary cyclosporin A excretion was studied in rats. Infusion of both taurocholate and tauroursodeoxycholate at the rate of 0.8 mmol/min per 100 g bodyweight increased bile flow and biliary cyclosporin A excretion, and the extent was more prominent with tauroursodeoxycholate. It was suggested that these findings were caused by the enhanced vesicular targeting of P-gp to the canalicular membrane by bile acids, thus increasing the numbers of P-gp in the canalicular membrane.
Department of Medicine, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, 173-8605, Tokyo, Japan
H
H
Takikawa
N
N
Sano
Y
Y
Takada
A
A
Toda
H
H
Tanaka
Y
Y
Takamori