Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats

Abstract

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.

Effects of Organic Anions and Vinblastine on Biliary Excretion of Erythromycin in Rats

“…PTZ treatment results in an increased expression of P-GP [26]. This may imply that BSP is a substrate of P-GP, although this might represent a minor pathway for the anionic dye [35]. It can not be excluded therefore that BSP competed with EM transport by P-GP in the present study.…”

“…We have previously reported that biliary BSP excretion was increased by PTZ treatment [35]. PTZ treatment results in an increased expression of P-GP [26].…”

Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats

“…Male Sprague–Dawley rats were purchased from Japan Laboratory Animals (Tokyo, Japan), and all experiments were carried out using rats each weighing approximately 270 g after overnight fasting. Colchicine (0.2 mg/100 g) was injected intraperitoneally 3 h before the administration of various compounds 16 . Animals were anesthetized with an intraperitoneal injection of pentobarbital (5 mg/100 g), and the common bile duct was cannulated with PE‐10 tubing (Becton Dickinson Primary Care Diagnostics, Sparks, MD, USA) after laparotomy.…”

“…Colchicine has also been reported to inhibit the biliary excretion of some organic anions 13–16 . However, the findings of the effect of colchicine on biliary excretion are controversial 13–16 …”

Bioactive Phenothiazines and Benzo[a]phenothiazines: Spectroscopic Studies, and Biological and Biomedical Properties and Applications

“…Takikawa et al [178] compared the effects of colchicine and phenothiazine, applied as substrates for P-glycoprotein, on the vesicular transport and biliary excretion of some organic anions in rats. The colchicine treatment slightly inhibited the biliary excretion of indocyanine green, dinitrophenyl glutathione and pravastatin, but this treatment had no effect on the biliary excretion of sulphobromophthalein and dibromosulphophthalein.…”