Title

Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20)

Document Type

Article

Original Publication Date

2006

Journal/Book/Conference Title

American Journal of Physiology - Renal Physiology

Volume

291

Issue

2

First Page

F314

Last Page

F321

DOI of Original Publication

10.1152/ajprenal.00497.2005

Comments

Originally published at doi:10.1152/ajprenal.00497.2005

PMCID: PMC2825707 NIHMSID: NIHMS174820 Douglas H. Sweet was at Medical University of South Carolina at the time of publication.

Date of Submission

October 2015

Abstract

Recently, a novel Slc22 gene family member expressed in murine olfactory mucosa was identified and based on sequence homology proposed to be an organic anion transporter [Oat6 (Slc22a20); J. C. Monte, M. A. Nagle, S. A. Eraly, and S. K. Nigam. Biochem Biophys Res Commun 323: 429–436, 2004]. However, no functional data for Oat6 was reported. In the present study, we demonstrate that murine Oat6 mediates the inhibitable transport of estrone sulfate using both Xenopus oocyte expression assay and Chinese hamster ovary (CHO) cells stably transfected with mOat6 (CHO-mOat6). Uptake was virtually eliminated by probenecid and the anionic herbicide 2,4-dichlorophenoxyacetate. The organic anions ochratoxin A, salicylate, penicillin G, p-aminohippurate, and urate inhibited mOat6-mediated accumulation to varying degrees. Transport of estrone sulfate by mOat6 was demonstrated to be saturable, and Km estimates of 109.8 ± 22.6 μM in oocytes and 44.8 ± 7.3 μM in CHO-mOat6 cells were obtained. Inhibitory constants for 2,4-dichlorophenoxyacetate (15.7 ± 2.0 μM), salicylate (49.0 ± 4.4 μM), probenecid (8.3 ± 2.5 μM), and penicillin G (1,450 ± 480 μM) were also determined. Accumulation of estrone sulfate mediated by mOat6 was significantly trans-stimulated by glutarate, indicating that mOat6 functions as an organic anion/dicarboxylate exchanger. These data demonstrate for the first time that the novel murine gene Oat6(Slc22a20) encodes a functional organic anion transporter and mOat6 is indeed the newest member of the OAT gene family.

Rights

Copyright © 2006 the American Physiological Society

Is Part Of

VCU Pharmaceutics Publications

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