Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes

被引:69
作者
Okuda, M [1 ]
Urakami, Y [1 ]
Saito, H [1 ]
Inui, K [1 ]
机构
[1] Kyoto Univ, Fac Med, Kyoto Univ Hosp, Dept Pharm,Sakyo Ku, Kyoto 6068507, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 1999年 / 1417卷 / 02期
关键词
organic cation transporter; OCT1; OCT2; renal tubular secretion; (Xenopus oocyte);
D O I
10.1016/S0005-2736(99)00005-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The molecular mechanisms of organic cation transport by rat OCT2 was examined in the Xenopus oocyte expression system. When extracellular Na+ ions were replaced with K+ ions, uptake of tetraethylammonium (TEA) by OCT2-expressing oocytes was decreased, suggesting that TEA uptake by OCT2 is dependent on membrane potential. Kinetic analysis revealed that the decreased TEA uptake by ion substitution was caused at least in part by decreased substrate affinity. Acidification of extracellular buffer resulted in decreased uptake of TEA, whereas TEA efflux from OCT1- and OCT2-expressing oocytes was not stimulated by inward proton gradient, in consistent with basolateral organic cation transport in the kidney. Inhibition of TEA uptake by various organic cations revealed that apparent substrate spectrum of OCT2 was similar with that of OCT1. However. the affinity of procainamide to OCT1 was higher than that to OCT2. Uptake of 1-methyl-4-phenylpyridinium was stimulated by OCT2 as well as OCT1. but uptake of levofloxacin. a zwitterion, was not stimulated by both OCTs. These results suggest that OCT2 is a multispecific organic cation transporter with the characteristics comparable to those of the basolateral organic cation transporter in the kidney. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:224 / 231
页数:8
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