Biochemical and molecular pharmacological aspects of transporters as determinants of drug disposition.
Biochemical and molecular pharmacological aspects of transporters as determinants of drug disposition.
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DOI：
10.2133/dmpk.20.91
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发表时间：
2005-04-01
影响因子：
2.1
通讯作者：
Sai, Yoshimichi
中科院分区：
文献类型：
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作者：
Sai, Yoshimichi
膜转运蛋白是典型地具有12个跨膜结构域的整合膜蛋白。大多数SLC家族转运蛋白由300-800个氨基酸残基组成，分子量为40-90 kDa，而ABC家族转运蛋白的相应值分别为1，200 - 1，500个残基和140-180 kDa。每种转运蛋白都具有特征性的组织分布和亚细胞定位。我分离了寡肽转运蛋白PEPT 1、单羧酸转运蛋白MCT 1和有机阳离子/肉毒碱转运蛋白（OCTNs）等多种转运蛋白的cDNA，并确定了它们的组织分布和亚细胞定位。我还确定了转运蛋白的绝对表达水平，以评估其在各种组织中对药物转运的相对贡献。重要的是要注意，转运蛋白的表达水平可以在各种生理条件下和通过给药而改变。表达水平、亚细胞定位和功能特性的变化都可能参与药物药代动力学的个体间差异。转运蛋白是药物处置的关键决定因素之一。
Membrane transporters are integral membrane proteins typically having 12 transmembrane domains. Most of the SLC family transporters consist of 300-800 amino acid residues with a molecular mass of 40-90 kDa, while the corresponding values of ABC family transporters are 1,200-1,500 residues and 140-180 kDa, respectively. Each transporter has a characteristic tissue distribution and subcellular localization. I have isolated cDNAs of various transporters, including oligopeptide transporter PEPT1, monocarboxylic acid transporter MCT1 and organic cation/carnitine transporters (OCTNs), and determined their tissue distribution and subcellular localization. I have also determined the absolute expression levels of transporters to evaluate their relative contributions to drug transport in various tissues. It is important to note that expression levels of transporters can be changed under various physiological conditions and by administration of drugs. Changes in expression level, subcellular localization and functional properties can all be involved in inter-individual differences in drug pharmacokinetics. Transporters are among the key determinants of drug disposition.