341 EXPRESSION OF DIFFERENT ISOFORMS OF MDR3 FROM HUMAN LIVER

(+126±18%, p 200 per group, n = 3–4), E17G diminished cVA of CLF to 36±3% of control values (p < 0.01), and pretreatment with PD and SB partially attenuated this decrease (57±2% and 56±1%, respectively; p < 0.05). Protection was even higher when both inhibitors were co-administered (77±2%, p < 0.05), suggesting complementarity between p38 and ERK1/2. cVA of GS-MF showed a similar pattern of change. Conclusions: E17G-induced cholestasis involves cooperative activation of cPKC/p38 and PI3K/Akt/ERK1/2 signaling pathways. Whereas cPKC/p38 mediates endocytic internalization of canalicular transporters, PI3K/Akt/ERK1/2 favors their intracellular retention.