Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.
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Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T
Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.
Mol Pharmacol. 2002 Jul;62(1):7-14.
- PubMed ID
- 12065749 [ View in PubMed]
- Abstract
We isolated cDNA encoding a multispecific organic anion transporter 2 (OAT2) from the mouse kidney cDNA library. Isolated mouse OAT2 (mOAT2) consisted of 1623 base pairs that encoded a 540-amino acid residue protein with 12 putative membrane-spanning domains, and the amino acid sequence was 87% identical to that of rat OAT2 (rOAT2). The gene coding for mOAT2, Slc22a7, is found on chromosome 17C. Northern blot analysis revealed that the mOAT2 mRNA is abundantly expressed in the male mouse kidney, whereas it was predominantly expressed in both the liver and kidney of female mice. When expressed in Xenopus laevis oocytes, mOAT2 mediated the high affinity transport of glutarate (K(m) = 15.8 +/- 3.2 microM) and prostaglandin E2 (K(m) = 5.2 +/- 0.5 nM) in a sodium-independent manner. mOAT2-expressing oocytes also mediated the uptake of alpha-ketoglutarate, glutarate, prostaglandin E2, p-aminohippuric acid, methotrexate, ochratoxin A, valproate, and allopurinol. However, we did not observe mOAT2-mediated uptake of salicylate. A wide range of structurally unrelated organic anions inhibited mOAT2-mediated glutarate uptake especially erythromycin, a potent inhibitor. These results indicate that isolated mOAT2 is a multispecific organic anion transporter having some differences in substrate specificity compared with rOAT2. In addition, we found that there exists a sex- and species-related differential gene expression of the OAT2 isoform.
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- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Allopurinol Solute carrier family 22 member 7 Protein Humans UnknownSubstrateDetails Aminohippuric acid Solute carrier family 22 member 7 Protein Humans UnknownSubstrateDetails Cefoperazone Solute carrier family 22 member 7 Protein Humans UnknownInhibitorDetails Cimetidine Solute carrier family 22 member 7 Protein Humans UnknownSubstrateInhibitorDetails Dinoprostone Solute carrier family 22 member 7 Protein Humans UnknownSubstrateInhibitorDetails Enalapril Solute carrier family 22 member 7 Protein Humans UnknownInhibitorDetails Glutaric Acid Solute carrier family 22 member 7 Protein Humans UnknownSubstrateDetails Salicylic acid Solute carrier family 22 member 7 Protein Humans UnknownSubstrateDetails Valproic acid Solute carrier family 22 member 7 Protein Humans UnknownSubstrateDetails