P-Glycoprotein expression in human, mouse, hamster and rat hepatocytes in primary culture

P-Glycoprotein (P-gp), the multidrug resistance (MDR) gene product,has previously been shown to be functional and overexpressedin adult rat hepatocytes during primary culture. In the presentstudy, we examined P-gp expression in human, mouse and hamsterhepatocytes cultured in conditions similar to those used forrat liver cells. Northern blotting and doxorubicin P-gp-mediatedefflux analyses revealed that liver parenchymal cells from thesethree species exhibited only limited increased MDR mRNA levelswith no intracellular decreased drug retention, thus suggestingthat the marked functional P-gp induction observed in rat hepatocytescould reflect a species-specific response of these cells toan unfamiliar environment. An 8 h exposure to cycloheximide,which strongly induced MDR mRNAs in rat liver cells, also increased,although to a far lesser extent, MDR mRNA levels in human, mouseand hamster hepatocytes, indicating that P-gp expression innormal liver parenchymal cells could be at least partly negativelyregulated by a labile protein factor.