American Journal of Physiology: Renal, Fluid & Electrolyte Physiology (Abstracts) 2015-11-15

Human organic anion transporter 2 is distinct from organic anion transporters 1 and 3 with respect to transport function.

Maja Henjakovic, Yohannes Hagos, Wolfgang Krick, Gerhard Burckhardt, Birgitta C Burckhardt

Index: Am. J. Physiol. Renal Physiol. 309 , F843-51, (2015)

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Abstract

Phylogentically, organic anion transporter (OAT)1 and OAT3 are closely related, whereas OAT2 is more distant. Experiments with human embryonic kidney-293 cells stably transfected with human OAT1, OAT2, or OAT3 were performed to compare selected transport properties. Common to OAT1, OAT2, and OAT3 is their ability to transport cGMP. OAT2 interacted with prostaglandins, and cGMP uptake was inhibited by PGE2 and PGF2α with IC50 values of 40.8 and 12.7 μM, respectively. OAT1 (IC50: 23.7 μM), OAT2 (IC50: 9.5 μM), and OAT3 (IC50: 1.6 μM) were potently inhibited by MK571, an established multidrug resistance protein inhibitor. OAT2-mediated cGMP uptake was not inhibited by short-chain monocarboxylates and, as opposed to OAT1 and OAT3, not by dicarboxylates. Consequently, OAT2 showed no cGMP/glutarate exchange. OAT1 and OAT3 exhibited a pH and a Cl- dependence with higher substrate uptake at acidic pH and lower substrate uptake in the absence of Cl-, respectively. Such pH and Cl- dependencies were not observed with OAT2. Depolarization of membrane potential by high K+ concentrations in the presence of the K+ ionophore valinomycin left cGMP uptake unaffected. In addition to cGMP, OAT2 transported urate and glutamate, but cGMP/glutamate exchange could not be demonstrated. These experiments suggest that OAT2-mediated cGMP uptake does not occur via exchange with monocarboxylates, dicarboxylates, and hydroxyl ions. The counter anion for electroneutral cGMP uptake remains to be identified.Copyright © 2015 the American Physiological Society.