Further Characterization of the Electrogenicity and pH Sensitivity of the Human Organic Anion-Transporting

Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake of many endogenous and xenobiotic compounds, such as bile acids and drugs, respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma membrane potential () was investigated. In X. laevis oocytes, nonspecific plasma membrane permeability in-creased only at pHo below 4.5. Above this value, both using oocytes and CHO cells, extracellular acidification affected differ-ently the specific transport of taurocholic acid (TCA) and estradiol 17-D-glucuronide (E217G) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and OATP1B3 (stimulation). Changes in substrate up-take in the presence of valinomycin (K-ionophore), carbonyl cy