Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organicanion transporting polypeptide, oatp2

Purpose. We previously demonstrated the HMG-CoA reductase inhibitor, pravas tatin, is actively taken up into isolated rat hepatocytes through multispec ific organic anion transporters. The present study examined whether a newly cloned organic anion transporting polypeptide (oatp2) transports pravastat in. Methods. We investigated functional expression of oatp2 in Xenopus laevis o ocytes, to examine [C-14] pravastatin uptake. Results. [C-14] Pravastatin (30 mu M) uptake into oatp2 cRNA-injected oocyt es was 40 times higher than that of water-injected control oocytes. The oat p2-mediated pravastatin uptake was Na+-independent and saturable. The Micha elis-Menten constant was 37.5 +/- 9.9 mu M, a level comparable to that obta ined in isolated rat hepatocytes in our previous study. As is the case with rat hepatocytes, the uptake of pravastatin (30 mu M) was inhibited by 300 mu M concentrations of taurocholate. cholate, bromosulfophthalein. estradio l-17 beta-glucuronide, and simvastatin acid, but not by para-aminohippurate . On the other hand, [C-14] simvastatin acid (30 mu M) uptake of oatp2 cRNA -injected oocytes was not significantly different from that of water-inject ed oocytes. Conclusions. The cloned oatp2 was identified as the transporter responsible for the active hepatocellular pravastatin uptake.