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

Xiaohong Zhang, Carlotta E. Groves, Andrew Bahn, Wendy M. Barendt, Marcos D. Prado, Matthias Rödiger, Varanuj Chatsudthipong, Gerhard Burckhardt, Stephen Wright

Research output: Contribution to journalArticle

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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 μM) and did not support estrone sulfate (ES) transport, whereas OAT3 had a high affinity for ES (Kt of 4.5 μM) and a weak interaction with PAH (IC50 > 1 mM). In contrast, both transporters robustly accumulated OTA. Intact RPT also accumulated OTA, with OAT1 and OAT3 each responsible for ∼50%: ES and PAH each reduced uptake by ∼50%, and the combination of the two eliminated mediated OTA uptake. The weak base CIM was transported by OAT3 (Kt of 80 μM) and OCT2 (Kt of 2 μM); 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 the early proximal tubule than OCT1/2. In single S2 segments of RPT, ES and TEA each blocked ∼50% of CIM uptake. Thus the fractional contribution of different OE transporters to renal secretion is influenced by their affinity for substrate and relative expression level in RPT.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number5 56-5
DOIs
StatePublished - Nov 2004

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Cimetidine
Electrolytes
Proximal Kidney Tubule
Rabbits
Organic Anion Transporters
Inhibitory Concentration 50
Cultured Cells
estrone sulfate
Kidney
Acids
ochratoxin A

Keywords

  • Kidney

ASJC Scopus subject areas

  • Physiology

Cite this

Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule. / Zhang, Xiaohong; Groves, Carlotta E.; Bahn, Andrew; Barendt, Wendy M.; Prado, Marcos D.; Rödiger, Matthias; Chatsudthipong, Varanuj; Burckhardt, Gerhard; Wright, Stephen.

In: American Journal of Physiology - Renal Physiology, Vol. 287, No. 5 56-5, 11.2004.

Research output: Contribution to journalArticle

Zhang, Xiaohong ; Groves, Carlotta E. ; Bahn, Andrew ; Barendt, Wendy M. ; Prado, Marcos D. ; Rödiger, Matthias ; Chatsudthipong, Varanuj ; Burckhardt, Gerhard ; Wright, Stephen. / Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule. In: American Journal of Physiology - Renal Physiology. 2004 ; Vol. 287, No. 5 56-5.
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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 μM) and did not support estrone sulfate (ES) transport, whereas OAT3 had a high affinity for ES (Kt of 4.5 μM) and a weak interaction with PAH (IC50 > 1 mM). In contrast, both transporters robustly accumulated OTA. Intact RPT also accumulated OTA, with OAT1 and OAT3 each responsible for ∼50{\%}: ES and PAH each reduced uptake by ∼50{\%}, and the combination of the two eliminated mediated OTA uptake. The weak base CIM was transported by OAT3 (Kt of 80 μM) and OCT2 (Kt of 2 μM); 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 the early proximal tubule than OCT1/2. In single S2 segments of RPT, ES and TEA each blocked ∼50{\%} of CIM uptake. Thus the fractional contribution of different OE transporters to renal secretion is influenced by their affinity for substrate and relative expression level in RPT.",
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AU - Groves, Carlotta E.

AU - Bahn, Andrew

AU - Barendt, Wendy M.

AU - Prado, Marcos D.

AU - Rödiger, Matthias

AU - Chatsudthipong, Varanuj

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