Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule

American Journal of Physiology. Renal Physiology
Xiaohong ZhangStephen H Wright

Abstract

We compared the characteristics of several cloned rabbit organic electrolyte (OE) transporters expressed in cultured cells with their behavior in intact rabbit renal proximal tubules (RPT) to determine the contribution of each to basolateral uptake of the weak acid ochratoxin A (OTA) and the weak base cimetidine (CIM). The activity of organic anion transporters OAT1 and OAT3 proved to be distinguishable because OAT1 had a high affinity for PAH (K(t) of 20 microM) and did not support estrone sulfate (ES) transport, whereas OAT3 had a high affinity for ES (K(t) of 4.5 microM) and a weak interaction with PAH (IC(50) > 1 mM). In contrast, both transporters robustly accumulated OTA. Intact RPT also accumulated OTA, with OAT1 and OAT3 each responsible for approximately 50%: ES and PAH each reduced uptake by approximately 50%, and the combination of the two eliminated mediated OTA uptake. The weak base CIM was transported by OAT3 (K(t) of 80 microM) and OCT2 (K(t) of 2 microM); OCT1 had a comparatively low affinity for CIM, and CIM uptake by OAT1 was equivocal. Intact RPT accumulated CIM, with TEA and ES reducing CIM uptake by 20 and 75%, respectively, suggesting that OAT3 plays a quantitatively more significant role in CIM uptake in ...Continue Reading

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Citations

Oct 14, 2006·The Journal of Pharmacology and Experimental Therapeutics·Anand BalakrishnanJames E Polli
Aug 10, 2007·American Journal of Physiology. Renal Physiology·Adam L VanwertDouglas H Sweet
Jan 5, 2011·Biological Chemistry·Shivangi GuptaYohannes Hagos
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Mar 1, 2007·American Journal of Physiology. Renal Physiology·Sunhapas SoodvilaiVaranuj Chatsudthipong
Apr 20, 2007·American Journal of Physiology. Renal Physiology·Xiaohong ZhangStephen H Wright
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