EFFECTS OF PHALLOIDIN AND COLCHICINE ON DIETHYLMALEATE-INDUCED CHOLERESIS AND ULTRASTRUCTURAL APPEARANCE OF RAT HEPATOCYTES

Diethylmaleate is used as a model compound whose glutathione conjugate s are secreted into bile, and which induce choleresis and the formatio n of Golgi-derived vesicles in hepatocytes. This study was performed t o test the assumption that these vesicles are involved in the bile can alicular secretion of diethylmaleate. We reasoned that phalloidin and colchicine, two drugs acting on microfilaments and microtubules, respe ctively, can modify the movements of diethylmaleate-induced vesicles t owards the bile canaliculus. Phalloidin induced the formation of a thi ck microfilamentous network around the bile canalicular plasma membran e domain. A significant decrease in diethylmaleate-stimulated choleres is was observed, associated with a striking accumulation of pericanali cular vesicles, which were confirmed by morphometric analysis. In cont rast, in rats pretreated with colchicine, after diethylmaleate adminis tration, only a few vesicles were observed around the bile canaliculus , while diethylmaleate-induced choleresis also decreased. These result s suggest that: a) the thick microfilament network induced by phalloid in prevents diethylmaleate-associated vesicles reaching the bile canal icular plasma membrane; and b) colchicine produces a dispersion of the se vesicles in the cytoplasm of hepatocytes by inhibiting the polymeri zation of microtubules. These observations support a role of vesicles in the transport of diethylmaleate by hepatocyte into bile, and are co nsistent with the existence of a vesicular pathway for the biliary sec retion of diethylmaleate and possibly other organic anions.