INFLUENCE OF COLCHICINE AND PHALLOIDIN ON BILE SECRETION AND HEPATIC ULTRASTRUCTURE IN THE RAT - POSSIBLE INTERACTION BETWEEN MICROTUBULES AND MICROFILAMENTS
The role of microtubules and microfilaments on bile secretion in the rat in vivo was examined. Phalloidin (which causes irreversible polymerization of actin into microfilaments), administered at the dose of 50 .mu.g/100 g body wt during 3 days, caused an increase in the microfilamentous network around bile canaliculi; it induced a significant decrease 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 h 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 has no effect on tubulin, had no effect on bile secretion. The combined administration of phalloidin and colchicine caused 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. The effects of the 2 drugs apparently were not simply additive, but synergic. Although a toxic effect of colchicine could not be totally excluded, microtubules as well as microfilaments apparently play a role in the excretion of a bile-acid load.