ORGANIC CATION-TRANSPORT BY RAT-LIVER LYSOSOMES

被引:27
作者
MOSELEY, RH [1 ]
VANDYKE, RW [1 ]
机构
[1] UNIV MICHIGAN, SCH MED, ANN ARBOR, MI 48105 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1995年 / 268卷 / 03期
关键词
TETRAETHYLAMMONIUM; PROTON-ADENOSINE-TRIPHOSPHATASE; ORGANIC CATION PROTON EXCHANGE; HEPATIC DRUG DISPOSITION; BILIARY EXCRETION;
D O I
10.1152/ajpgi.1995.268.3.G480
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Hepatic organic cation transport has been characterized in rat Liver plasma membrane vesicles, using the quaternary amine tetraethylammonium (TEA) as a model substrate. Sinusoidal TEA uptake is stimulated by an inside-negative membrane potential; TEA transport across the canalicular membrane is mediated by electroneutral organic cation-Hi exchange. Substrates for these transport processes include procainamide ethobromide (PAEB) and vecuronium, cationic drugs that undergo biliary excretion. Given the apparent absence of sinusoidal transport mechanisms able to generate high hepatocyte-to-blood organic cation concentration ratios, intracellular transport of organic cations may involve sequestration and concentration within acidified organelles. Therefore, the characteristics of TEA uptake were examined in isolated rat Liver lysosomes that are acidified by a well-described H+-adenosinetriphosphatase (ATPase). Lysosomal uptake of [C-14]TEA was a time- and ATP-dependent process, reaching steady state after 30-60 min. Steady-state [C-14]TEA uptake was significantly reduced by omission of ATP and by addition of monensin, conditions that alter lysosomal pH and membrane potential gradients, and by the H+-ATPase inhibitors, N-ethylmaleimide and bafilomycin A. ATP-dependent lysosomal [C-14]TEA uptake was significantly inhibited by PAEB, vecuronium, and other organic cationic substrates of canalicular TEA/H+ exchange. These findings demonstrate that rat liver lysosomes sequester certain organic cationic drugs, most likely via organic cation/H+ exchange driven by H+-ATPase. Canalicular organic cation/H+ exchange may reflect, in part, the exocytic insertion of this transporter from an intracellular compartment to this membrane domain.
引用
收藏
页码:G480 / G486
页数:7
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