Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.
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.
Kobayashi
Yasuna
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Ohshiro
Naomi
N
Shibusawa
Akiko
A
Sasaki
Tadanori
T
Tokuyama
Shogo
S
Sekine
Takashi
T
Endou
Hitoshi
H
Yamamoto
Toshinori
T
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; C490281:Slc22a7 protein, mouse