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Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats
Author(s) -
TAKIKAWA HAJIME,
SANO NAOYO,
AKIMOTO KAZUKO,
OGASAWARA TAKASHI,
YAMANAKA MASAMI
Publication year - 1998
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1998.tb00658.x
Subject(s) - excretion , organic anion , phenothiazine , glutathione , colchicine , p glycoprotein , organic anion transporting polypeptide , multidrug resistance associated protein 2 , medicine , intracellular , chemistry , biochemistry , endocrinology , transporter , pharmacology , atp binding cassette transporter , ion , enzyme , organic chemistry , multiple drug resistance , gene , antibiotics
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, dinitrophenylglutathione 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.