Differential regulation of canalicular multispecific organic anion transporter (cMOAT) expression by the chemopreventive agent oltipraz in primary rat hepatocytes and in rat liver

Expression of the canalicular multispecific organic anion transporter (cMOA T), an efflux pump involved in biliary secretion of xenobiotics, was invest igated in rat hepatocytes exposed to the chemopreventive agent oltipraz, No rthern blotting indicated that this compound increased cMOAT mRNA levels in primary cultured hepatocytes, Such an induction of cMOAT transcripts was d emonstrated to be dose-dependent and started as early as 4 h treatment; in addition, western blotting showed increased levels of 190 kDa cMOAT in olti praz-treated primary rat hepatocytes when compared with their untreated cou nterparts, In contrast, administration of oltipraz to rats failed to enhanc e hepatic cMOAT mRNA and protein amounts whereas it was found to induce liv er expression of glutathione S-transferase pi, a well-known oltipraz-regula ted drug metabolizing enzyme. These data therefore suggest that cMOAT up-re gulation occurring in rat hepatocytes in response to oltipraz may be restri cted to in vitro situations and is therefore unlikely to be directly involv ed in the in vivo chemopreventive properties of oltipraz.