Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats.
Vesicular transport inhibitors have been reported to inhibit biliary excretion of some organic anions, suggesting that vesicular transport has a role in intracellular transport of these compounds. However, these inhibitors are substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in canalicular transport of organic anions in addition to the canalicular multispecific organic anion transporter, we studied the effect of colchicine, a vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein expression on biliary excretion of various organic anions in rats. Colchicine treatment slightly but significantly inhibited biliary excretion of indocyanine green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine treatment did not affect biliary excretion of indocyanine green and pravastatin, but it increased biliary sulphobromophthalein-glutathione excretion. In conclusion, the present findings suggest that P-glycoprotein plays an additive role on biliary excretion of some organic anions in addition to the canalicular multispecific organic anion transporter.
Takikawa
H
H
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Sano
N
N
Akimoto
K
K
Ogasawara
T
T
Yamanaka
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004137:Dinitrochlorobenzene / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013448:Sulfobromophthalein / Q000493:pharmacokinetics
C042630:1-chloro-2,4-dinitrobenzene-glutathione conjugate; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004396:Coloring Agents; D004137:Dinitrochlorobenzene; D010640:Phenothiazines; D013448:Sulfobromophthalein; C012479:dibromosulphthalein; D005978:Glutathione; C031637:phenothiazine; D007208:Indocyanine Green; D003078:Colchicine