Hepatic Sinusoidal membrane transport of anionic drugs mediated by anion transporter npt

Hikaru Yabuuchi, Ikuml Tamai, Kyoko Morita, Tomoko Kouda, Ken Ichi Miyamoto, Eiji Takeda, Akira Tsuji

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68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1391-1396
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume286
Issue number3
Publication statusPublished - 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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