title: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1.
abstract: 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, alpha-ketoglutarate, and probenecid was characterized. The IC(50) values of many inhibitors were similar for both transporters, whereas others were significantly different. Mepiperphenidol and O-methylisoprenaline showed an approximately 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.
authors.affiliation: Institute of Anatomy of the Bayerische Julius-Maximilians-Universität, Koellikerstr. 6, 97070 Würzburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Arndt
authors.forename: C
authors.initials: C
authors.lastname: Volk
authors.forename: V
authors.initials: V
authors.lastname: Gorboulev
authors.forename: T
authors.initials: T
authors.lastname: Budiman
authors.forename: C
authors.initials: C
authors.lastname: Popp
authors.forename: I
authors.initials: I
authors.lastname: Ulzheimer-Teuber
authors.forename: A
authors.initials: A
authors.lastname: Akhoundova
authors.forename: S
authors.initials: S
authors.lastname: Koppatz
authors.forename: E
authors.initials: E
authors.lastname: Bamberg
authors.forename: G
authors.initials: G
authors.lastname: Nagel
authors.forename: H
authors.initials: H
authors.lastname: Koepsell
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002794:Choline / Q000494:pharmacology; D003001:Cloning, Molecular; D005260:Female; D019791:Guanidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D018408:Patch-Clamp Techniques; D011803:Quinine / Q000493:pharmacokinetics*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D000838:Anions; D002352:Carrier Proteins; D002412:Cations; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D011994:Recombinant Proteins; C491013:SLC22A2 protein, human; C100590:Slc22a2 protein, rat; D019789:Tetraethylammonium; D006632:Histamine; D011803:Quinine; D019791:Guanidine; D002794:Choline