Effects of phalloidin on the biliary excretion of cholephilic compounds in rats.
Phalloidin is known to cause cholestasis by preventing microfilament depolymerization. In addition, phalloidin is reported to inhibit the vesicular targeting of canalicular transporters. The aim of the present study was to examine the effect of phalloidin on the biliary excretion of substrates typical for various canalicular transporters in rats. Phalloidin decreased the biliary excretion of tracer amounts of taurocholate, leukotriene C(4), pravastatin, and vinblastine. Increases in bile flow and biliary bile acid excretion caused by taurocholate infusion were completely inhibited by phalloidin. These data indicate that, in addition to multidrug resistance protein 2 and P glycoprotein, the vesicular targeting of the bile salt export pump, a major canalicular bile acid transporter, is also impaired by phalloidin. The decrease of biliary excretion of glutathione may also relate to the increase in the bile acid independent canalicular bile flow in phalloidin-treated rats.
Ohashi
Masaki
M
Department of Medicine, Teikyo University School of Medicine, Itabashi, Tokyo, Japan.
Sano
Naoyo
N
Takikawa
Hajime
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D002756:Cholagogues and Choleretics / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis / Q000187:drug effects; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010590:Phalloidine / Q000494:pharmacology*; D017035:Pravastatin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000378:metabolism; D014747:Vinblastine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000924:Anticholesteremic Agents; D002756:Cholagogues and Choleretics; D005978:Glutathione; D017997:Leukotriene C4; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010590:Phalloidine; D017035:Pravastatin; D013656:Taurocholic Acid; D014747:Vinblastine; C421109:multidrug resistance-associated protein 1