Human organic anion transporter 3 (hOAT3) can operate as an exchanger and mediate secretory urate flux.
OBJECTIVE
Renal secretion of organic anions is critically dependent on their basolateral uptake against the electrochemical gradient. Due to their localization, two transporters are likely involved, namely OAT1 and OAT3. While OAT1 as an exchanger clearly operates in the secretory direction, OAT3 in its previously supposed mode as a uniporter should move anionic substrates from cell to blood. It would thus dissipate gradients established by OAT1 of common OAT1/OAT3 substrates. In the present study we therefore reinvestigated the driving forces of human OAT3.


METHODS
The human OAT3 obtained Xenopus laevis oocyte expression system, hOAT3-mediated transport of estrone sulfate (ES) and dicarboxylates was assayed for cis-inhibition and/or trans-stimulation in both the uptake and efflux direction.


RESULTS
hOAT3-mediated efflux of glutarate (GA), can be significantly trans-stimulated by a variety of ions with high cis-inhibitory potency, including GA (282%), alpha-ketoglutarate (476%), p-aminohippurate (179%), and, most notably, urate (167%). Urate cis-inhibited ES uptake with an IC(50) close to normal serum urate concentrations.


CONCLUSIONS
These data indicate that OAT3 does not represent a uniporter but operates as an organic ion%dicarboxylate exchanger similar to OAT1, and may mediate renal urate secretion.
Bakhiya
Adiya
A
Zentrum Physiologie und Pathophysiologie, Georg-August-Universität, Göttingen.
Bahn
Andrew
A
Burckhardt
Gerhard
G
Wolff
Natascha
N
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002952:Citric Acid Cycle; D029382:Dicarboxylic Acid Transporters / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018075:RNA, Complementary / Q000235:genetics / Q000502:physiology; D014527:Uric Acid / Q000378:metabolism* / Q000494:pharmacology
D029382:Dicarboxylic Acid Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D018075:RNA, Complementary; C114338:organic anion transport protein 3; D014527:Uric Acid; D004970:Estrone; C017296:estrone sulfate