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