Characterization of mouse organic anion transporter 5 as a renal steroid sulfate transporter.
A family of organic anion transporters (OAT) recently identified has important roles for the excretion or reabsorption of endogenous and exogenous compounds, and several new isoforms have been reported in this decade. Although the transepithelial transport properties of organic anions are gradually being understood, many portions of their functional characteristics in functions remain to be elucidated. A recently reported new cDNA encoding a mouse OAT5 (mOAT5) was constructed, using 3'-RACE PCR, with the total RNA isolated from a mouse kidney. When mOAT5 was expressed in Xenopus oocytes, mOAT5 transported estrone sulfate, dehydroepiandrosterone sulfate and ochratoxin A. Estrone sulfate uptake by mOAT5 displayed a time-dependent and sodium-independent manner. The Km values of estrone sulfate and dehydroepiandrosterone sulfate were 2.2 and 3.8 microM, respectively. mOAT5 interacted with chemically heterogeneous steroid or organic sulfates, such as nitrophenyl sulfate, methylumbelliferyl sulfate and estradiol sulfates. In contrast to the sulfate conjugates, mOAT5-mediated estrone sulfate uptake was not inhibited by the steroid or organic glucuronides. The mOAT5 protein having about 85 kDa molecular weight was shown to be mainly localized in the apical membrane of the proximal tubules of the outer medulla. These results suggest an important role of mOAT5 for the excretion or reabsorption of steroid sulfates in the kidney.
Kwak
Jin-Oh
JO
Department of Pharmacology and Toxicology, College of Medicine, Inha University, 7-241 Shinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea.
Kim
Hyun-Woo
HW
Oh
Kwang-Jin
KJ
Ko
Chang-Bo
CB
Park
Hwayong
H
Cha
Seok Ho
SH
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D020719:Glucuronides / Q000737:chemistry; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009793:Ochratoxins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters / Q000737:chemistry*; D012313:RNA / Q000378:metabolism; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D014981:Xenopus
D002352:Carrier Proteins; D018076:DNA, Complementary; D020719:Glucuronides; D009793:Ochratoxins; D027361:Organic Anion Transporters; C488753:Slc22a19 protein, mouse; D013431:Sulfates; C025589:ochratoxin A; D004970:Estrone; D019314:Dehydroepiandrosterone Sulfate; D012313:RNA; C017296:estrone sulfate