Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms

J Pharmacol Sci. 2011;115(2):249-53. doi: 10.1254/jphs.10228sc. Epub 2011 Jan 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacokinetics
  • Biological Transport
  • Bumetanide / pharmacokinetics
  • Cell Membrane / metabolism
  • Diuretics / pharmacokinetics
  • Estrone / analogs & derivatives
  • Estrone / pharmacokinetics
  • Humans
  • Oocytes
  • Polymorphism, Single Nucleotide*
  • Sodium-Phosphate Cotransporter Proteins, Type I / genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type I / metabolism*
  • Uric Acid / pharmacokinetics
  • Xenopus
  • p-Aminohippuric Acid / metabolism

Substances

  • Antioxidants
  • Diuretics
  • SLC17A3 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type I
  • Bumetanide
  • Uric Acid
  • Estrone
  • estrone sulfate
  • p-Aminohippuric Acid