Influence of colchicine and phalloidin on bile secretion and hepatic ultrastructure in the rat. Possible interaction between microtubules and microfilaments.

The studies were carried out to examine the role of microtubules and microfilaments on bile secretion in the rat in vivo. Phalloidin (which causes irreversible polymerization of actin into microfilaments), administered at the dose of 50 microgram/100 g body wt during 3 days, caused an increase in the microfilamentous network around bile canaliculi; it induced a significant decrease both in basal bile flow, and in bile flow stimulated by sodium taurocholate, the major bile acid in the rat. Colchicine (which inhibits the polymerization of tubulin into microtubules), 3 hr after an injection of 0.2 mg/100 g body wt, caused the almost complete disappearance of microtubules in the hepatocytes; it did not modify basal bile secretion, but did induce a significant decrease in taurocholate secretion and taurocholate-stimulated bile flow after a bile-acid load, as well as a delayed plasma disappearance of the bile acid. Lumicolchicine, which is known to have no effect on tubulin, had no effect on bile secretion. The combined administration of phalloidin and colchicine caused both the increase of the pericanalicular microfilamentous network and the disappearance of microtubules; it induced a decrease in basal bile flow that was more marked than that observed with phalloidin alone, suggesting that the effects of the two drugs were not simply additive, but synergic. Although a toxic effect of colchicine could not be totally excluded, the results are compatible with the hypothesis that microtubules as well as microfilaments play a role in the excretion of a bile-acid load.