Biliary excretion of taurolithocholate-sulfate and temocaprilat in cholestatic rats induced by bile duct-ligation and ethinylestradiol.
Down-regulation of multidrug resistance protein 2 (Mrp2), a major canalicular organic anion transporter, has been reported in various cholestatic models and in patients with cholestasis. In the present study, biliary excretion of taurolithocholate-sulfate and temocaprilat, substrates of Mrp2, was studied in bile duct-ligated rats and in cholestatic rats induced by ethinylestradiol (EE). Biliary excretion of temocaprilat was more markedly decreased in bile duct-ligated rats than that of taurolithocholate-sulfate. In contrast, biliary excretion of both compounds were similarly inhibited in EE-treated rat. Such difference of the degree of inhibition may have been caused by the different degree of the inhibition of unknown canalicular transporters other than Mrp2 in bile duct-ligated rats.
Takikawa
Hajime
H
Department of Medicine, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, 173, Tokyo, Japan
Sano
Naoyo
N
Onishi
Toshiki
T
Toda
Atsuko
A
Tanaka
Hiroyuki
H
Hojo
Makoto
M
Marumo
Tatsuyuki
T
Hanawa
Naoko
N
Tachizawa
Hideki
H
Nishikawa
Kou
K