title: Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
authors.forename: Promsuk
authors.initials: P
authors.lastname: Jutabha
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Atsuo
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Wako
authors.initials: W
authors.lastname: Urano
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics; D001692:Biological Transport; D002034:Bumetanide / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000378:metabolism; D004232:Diuretics / Q000493:pharmacokinetics; D004970:Estrone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D009865:Oocytes; D020641:Polymorphism, Single Nucleotide; D050609:Sodium-Phosphate Cotransporter Proteins, Type I / Q000235:genetics* / Q000378:metabolism*; D014527:Uric Acid / Q000493:pharmacokinetics; D014981:Xenopus; D010130:p-Aminohippuric Acid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004232:Diuretics; C493550:SLC17A3 protein, human; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D002034:Bumetanide; D014527:Uric Acid; D004970:Estrone; C017296:estrone sulfate; D010130:p-Aminohippuric Acid