Inhibitory effect of quinidine and quinine on the oatp1- and oatp2- mediated transport

Organic anion transporting polypeptides-1, 2 (oatp1, oatp2) mediate the sinusoidal uptake of many organic compounds, mainly anionic or steroidal compounds, into rat hepatocytes. These two transporters have partially overlapping substrate specificities. It is one of the possible ways to calculate the contribution of oatp1 or oatp2 to the total uptake in rat hepatocytes to measure the uptake in rat hepatocytes while inhibiting specifically one of them. For this purpose, we aim to search for the specific inhibitors for oatp1 and oatp2. In this study, we measured the inhibitory effect of stereoisomers, quinidine and quinine. As a result, quinine inhibited oatp2-mediated transport at a lower concentration than oatp1-mediated transport while quinidine inhibited oatp1- and oatp2- mediated transport to a similar extent. The Ki value of quinine for the oatp2-mediated transport was less than 25 μ M while that for oatp1-mediated transport was about 100 μM. In a conclusion, quinine may be used as a selective inhibitor for oatp2-mediated transport at a low concentration.