Phalloidin alters bile canalicular contractility in primary monolayer cultures of rat liver.

We observed the motility of bile canaliculi in isolated rat hepatocytes obtained from animals that were pretreated with phalloidin (500 micrograms/kg body wt) for 1 and 3 days. Time-lapse cinephotomicrographs were taken in each experiment and in controls for 16.25 h. As we previously reported in normal hepatocytes, active contractions of bile canaliculi were observed. The number of contractions was 127.6 in controls, compared with 58.0 in 1-day phalloidin pretreated and 16.2 in 3-day phalloidin pretreated groups. The contraction process itself was not normal in the experimental groups, the contraction phase being slow and sustained. The altered canalicular motility depended on the dose of phalloidin administered. These results suggest that the integrity of actin filaments is necessary for normal bile canalicular motility. Further, dysfunction of actin microfilaments with altered canalicular motility may be involved in the pathogenesis of canalicular cholestasis.