TY - JOUR T1 - Hepatic Sinusoidal Membrane Transport of Anionic Drugs Mediated by Anion Transporter <em>Npt</em>1 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1391 LP - 1396 VL - 286 IS - 3 AU - Hikaru Yabuuchi AU - Ikumi Tamai AU - Kyoko Morita AU - Tomoko Kouda AU - Ken-Ichi Miyamoto AU - Eiji Takeda AU - Akira Tsuji Y1 - 1998/09/01 UR - http://jpet.aspetjournals.org/content/286/3/1391.abstract N2 - The purpose of our study was to establish the localization of the anion transporter Npt1 in liver and the relevance of Npt1 to carrier-mediated hepatic transport of β-lactam antibiotics. Immunocytochemical examination of mouse liver with antiserum forNpt1 showed basolateral (sinusoidal) membrane localization. Function of Npt1 was characterized in Xenopus laevis oocytes. Injection of in vitro-transcribed cRNA into oocytes resulted in an increased uptake of [14C]benzylpenicillin (PCG). The Npt1-mediated uptake was saturable with a Michaelis constant (Km ) of 0.46 ± 0.18 mM and a maximum rate (Vmax) of 46.6 ± 8.5 pmol/60 min/oocyte, and the uptake of [14C]PCG was independent of Na+ and pH, but dependent on chloride ion. Npt1-mediated [14C]PCG uptake was inhibited by several β-lactam antibiotics and probenecid. Oocytes injected with Npt1-cRNA demonstrated significantly enhanced transport activity for other anionic compounds such as [14C]faropenem, [14C]foscarnet and [3H]mevalonic acid, as well as [14C]PCG, compared with water-injected oocytes. In conclusion, Npt1 is suggested to participate in hepatic sinusoidal membrane transport of organic anions such as β-lactam antibiotics as well as inorganic anions for the efflux from hepatocyte-to-blood direction. The American Society for Pharmacology and Experimental Therapeutics ER -