The purpose of our study was to establish the localization of the anion transporter Npt1 in liver and the relevance of A/pf1 to carrier-mediated hepatic transport of β-lactam antibiotics. Immunocytochemical examination of mouse liver with antiserum for A/pf1 showed basolateral (sinusoidal) membrane localization. Function of A/pf1 was characterized in Xenopus laevis oocytes. Injection of in w'fro-transcribed cRNA into oocytes resulted in an increased uptake of [ 14C]benzylpenicillin (PCG). The Npf1 -mediated uptake was saturable with a Michaelis constant (K m) 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. A/pf1 -mediated [ 14C]PCG uptake was inhibited by several β-lactam antibiotics and probenecid. Oocytes injected with Npt 1 -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, A/pf1 is suggested to participate in hepatic sinusoidal membrane transport of organic anions such as -lactam antibiotics as well as inorganic anions for the efflux from hepatocyte-to-blood direction.
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1998|
All Science Journal Classification (ASJC) codes
- Molecular Medicine