Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-10-20
pubmed:abstractText
A novel member of the organic anion transporter (OAT) family, Oat5 (Slc22a19), has been reported to transport a naturally occurring mycotoxin, ochratoxin A (OTA). However, neither its endogenous substrate and driving force nor physiological functions have been determined. Herein, we report the functional characterization of rat Oat5 (rOat5), as well as its intrarenal distribution and membrane localization. When expressed in Xenopus laevis oocytes, rOat5 mediated the transport of sulfate conjugates of steroids such as estrone-3-sulfate (E(1)S; K(m) = 18.9 +/- 3.9 microM) and dehydroepiandrosterone sulfate (K(m) = 2.3 +/- 0.2 microM) in a sodium-independent manner, in addition to OTA. The rOat5-mediated E(1)S transport was strongly inhibited by four-carbon (C4) dicarboxylate succinate and longer dicarboxylates (C7-C9). The uptake of [(3)H]E(1)S via rOat5 was significantly trans-stimulated by succinate, and the efflux of [(14)C]succinate was significantly trans-stimulated by E(1)S. A similar trans-stimulatory effect of preloaded succinate on E(1)S uptake was also detected in cells stably expressing rOat5 (S(2) rOat5). rOat5 interacted with chemically heterogenous anionic compounds. The rOat5-mediated E(1)S transport was inhibited by several sulfate conjugates, such as 4-methylumbelliferyl sulfate and beta-estradiol sulfate, but not by glucuronide conjugates. An immunohistochemical study showed that rOat5 was localized at the apical membrane of renal proximal tubules in the corticomedullary region. rOat5 mRNA was expressed in the late segments (S(2) and S(3)) of proximal tubules. These results indicate that rOat5 is renal organic anion/dicarboxylates exchanger and, under physiological conditions, may function as an apical reabsorptive pathway for organic anions in proximal tubules driven by an outward gradient of dicarboxylates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
534-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16079298-Animals, pubmed-meshheading:16079298-Blotting, Western, pubmed-meshheading:16079298-Cell Membrane, pubmed-meshheading:16079298-Cells, Cultured, pubmed-meshheading:16079298-DNA, Complementary, pubmed-meshheading:16079298-Dehydroepiandrosterone Sulfate, pubmed-meshheading:16079298-Dicarboxylic Acid Transporters, pubmed-meshheading:16079298-Estrone, pubmed-meshheading:16079298-Expressed Sequence Tags, pubmed-meshheading:16079298-Immunohistochemistry, pubmed-meshheading:16079298-Kidney Tubules, Proximal, pubmed-meshheading:16079298-Kinetics, pubmed-meshheading:16079298-Membranes, pubmed-meshheading:16079298-Nephrons, pubmed-meshheading:16079298-Oocytes, pubmed-meshheading:16079298-RNA, Complementary, pubmed-meshheading:16079298-Rats, pubmed-meshheading:16079298-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16079298-Succinates, pubmed-meshheading:16079298-Transfection, pubmed-meshheading:16079298-Xenopus laevis
pubmed:year
2005
pubmed:articleTitle
Functional characterization of rat organic anion transporter 5 (Slc22a19) at the apical membrane of renal proximal tubules.
pubmed:affiliation
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't