Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions
Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions
复制标题
DOI：
10.1016/j.bbrc.2003.11.175
复制
发表时间：
2004-01-16
影响因子：
3.1
通讯作者：
Endou, H
中科院分区：
文献类型：
--
作者：
Sakata, T;Anzai, N;Endou, H
有机阳离子转运蛋白OCT 1（SLC 22 A1）在包括治疗重要药物在内的各种外源性物质的吸收、分布和排泄中起重要作用。在本研究中，我们分析了日本对照个体中发现的SLC 22 A1基因单核苷酸多态性（SNPs）的功能特性。在非洲爪蟾卵母细胞表达系统中，对导致氨基酸改变的四个突变（F160 L、P283 L、R287 G和P341 L）进行了功能表征。在日本人群中发现的两个新的SNPs P283 L和R287 G显示不摄取[C-14]TEA和[H-3]MPP+，尽管在注射了它们的cRNA的卵母细胞的质膜中检测到它们的蛋白表达。与野生型相比，P341 L对[C-14]TEA的摄取减少至65.1%，而F160 L的转运活性没有显著变化。这项研究表明，新发现的OCT 1变异体将有助于个体间的差异，导致阳离子药物处置的差异，也许某些疾病的过程。爱思唯尔公司出版
Organic cation transporter OCT1 (SLC22A1) plays an essential role in absorption, distribution, and excretion of various xenobiotics including therapeutically important drugs. In the present study, we analyzed the functional properties of the single nucleotide polymorphisms (SNPs) in SLC22A1 gene found in Japanese control individuals. Four mutations resulting in the amino acid changes (F160L, P283L, R287G, and P341L) were functionally characterized in Xenopus oocyte expression system. Two new SNPs, identified in Japanese population, P283L and R287G exhibited no uptake of both [C-14]TEA and [H-3]MPP+, although their protein expressions were detected in the plasma membrane of the oocytes injected with their cRNAs. Uptake of [C-14]TEA by P341L was reduced to 65.1% compared to wild type, whereas F160L showed no significant change in its transport activity. This study suggests that the newly found OCT1 variants will contribute to inter-individual variations leading to the differences in cationic drug disposition and perhaps certain disease processes. Published by Elsevier Inc.