Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1

American Journal of Physiology - Renal Physiology - Tập 281 Số 3 - Trang F454-F468 - 2001
Petra Arndt1, Christopher Volk1, Valentin Gorboulev1, Thomas Budiman2, Christian Popp1, I Ulzheimer-Teuber1, Aida Akhoundova1, Stefan Koppatz1, Ernst Bamberg2, Georg Nagel2, Hermann Koepsell1
1Institute of Anatomy of the Bayerische Julius-Maximilians-Universität, 97070 Würzburg; and
2Max-Planck-Institute of Biophysics, 60596 Frankfurt, Germany

Tóm tắt

The rat organic cation transporter (rOCT)-2 was characterized by electrical and tracer flux measurements compared with rOCT1. By applying choline gradients to voltage-clamped Xenopus oocytes expressing rOCT2, potential-dependent currents could be induced in both directions. Tracer flux measurements with seven organic cations revealed similar Michaelis-Menten constant values for both transporters, with the exception of guanidine. In parallel experiments with rOCT2 and rOCT1, inhibition of tetraethylammonium transport by 12 cations, 2 weak bases, corticosterone, and the anions para-amminohippurate, α-ketoglutarate, and probenecid was characterized. The IC50values of many inhibitors were similar for both transporters, whereas others were significantly different. Mepiperphenidol and O-methylisoprenaline showed an ∼70-fold lower and corticosterone a 38-fold higher affinity for rOCT2. With the use of these inhibitors together with previous information on cation transporters, experimental protocols are proposed to dissect out the individual contributions of rOCT2 and rOCT1 in intact proximal tubule preparations. Inhibition experiments at different pH levels strongly suggest that the weak base quinine passively permeates the plasma membrane at physiological pH and inhibits rOCT2 from the intracellular side.

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American Journal of Physiology - Renal Physiology

Tập 281 Số 3

F454-F468

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