Expression and functional characterization of murine organic anion transporting polypeptide 1b2 (oatp1b2/oatp4/lst‐1)

Abstract

The organic anion transporting polypeptide family plays important roles in mediating the cellular uptake of endogenous and exogenous compounds. Human liver enriched transporters such as OATP1B1 and OATP1B3 have been widely studied and shown to be involved in hepatic uptake and disposition of hormones, bile acids, and drugs. However, little is known about the murine orthologue, oatp1b2. Accordingly, expression of mouse oatp1b2 was assessed using real‐time PCR and Western blot analysis. mRNA transcripts were detected in a number of tissues including kidney, skeletal muscle, stomach and heart, with highest level in mouse liver. Immunohistochemical detection revealed localization of oatp1b2 in the sinusoidal membrane of hepatocytes. In contrast to the mRNA data, oatp1b2 protein expression was not detected in other tissues but liver. Cloning of the full coding region of oatp1b2 revealed the presence of two new splice variants. Interestingly, these variants were significantly expressed in the organs noted previously, but much less in liver. Heterologous expression experiments revealed taurocholic acid, estrone‐3‐sulfate, estradiol‐17β‐glucuronide, pravastatin and cerivastatin as substrates of the transporter. These findings give insights to species related differences in OATP transporter function that has application to mouse models of hepatic drug disposition.