Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
J Pharmacol Sci. 2011;115(2):249-53. doi: 10.1254/jphs.10228sc. Epub 2011 Jan 26.
We analyzed the functional properties of five nonsynonymous single nucleotide polymorphisms (SNPs) in the sodium-phosphate transporter NPT4 gene (SLC17A3) using the Xenopus oocyte expression system. NPT4 variants carrying SNP V257F, G279R, or P378L exhibited reduced transport of [(14)C]para-aminohippurate, [(3)H]bumetanide, [(3)H]estrone sulfate, and [(14)C]urate, when each variant clone was expressed in the plasma membrane of oocytes. This study suggests the possibility that the genetic variation of NPT4 contributes to inter-individual differences in disposition of anionic drugs such as diuretics as well as certain endogenous organic anions such as urate.
我们使用非洲爪蟾卵母细胞表达系统分析了钠离子-磷酸盐转运蛋白 NPT4 基因（SLC17A3）中五个非同义单核苷酸多态性（SNP）的功能特性。当 SNP V257F、G279R 或 P378L 变体的克隆被表达在卵母细胞膜上时，它们对 [(14)C]对氨基马尿酸、[(3)H]布美他尼、[(3)H]雌酮硫酸盐和 [(14)C]尿酸的转运能力降低。本研究提示 NPT4 的遗传变异可能导致个体间阴离子药物（如利尿剂）和某些内源性有机阴离子（如尿酸）处置的差异。
