TY - JOUR T1 - Human Neurons Express the Polyspecific Cation Transporter hOCT2, Which Translocates Monoamine Neurotransmitters, Amantadine, and Memantine JF - Molecular Pharmacology JO - Mol Pharmacol SP - 342 LP - 352 DO - 10.1124/mol.54.2.342 VL - 54 IS - 2 AU - Andreas E. Busch AU - Ulrich Karbach AU - Dagmar Miska AU - Valentin Gorboulev AU - Aida Akhoundova AU - Christopher Volk AU - Petra Arndt AU - Jochen C. Ulzheimer AU - Mark S. Sonders AU - Carmen Baumann AU - Siegfried Waldegger AU - Florian Lang AU - Hermann Koepsell Y1 - 1998/08/01 UR - http://molpharm.aspetjournals.org/content/54/2/342.abstract N2 - Recently, we cloned the human cation transporter hOCT2, a member of a new family of polyspecific transporters from kidney, and demonstrated electrogenic uptake of tetraethylammonium, choline, N1-methylnicotinamide, and 1-methyl-4-phenylpyridinium. Using polymerase chain reaction amplification, cDNA sequencing,in situ hybridization, and immunohistochemistry, we now show that hOCT2 message and protein are expressed in neurons of the cerebral cortex and in various subcortical nuclei. In Xenopus laevis oocytes expressing hOCT2, electrogenic transport of norepinephrine, histamine, dopamine, serotonin, and the antiparkinsonian drugs memantine and amantadine was demonstrated by tracer influx, tracer efflux, electrical measurements, or a combination. Apparent K m values of 1.9 ± 0.6 mm (norepinephrine), 1.3 ± 0.3 mm (histamine), 0.39 ± 0.16 mm (dopamine), 80 ± 20 μm(serotonin), 34 ± 5 μm (memantine), and 27 ± 3 μm (amantadine) were estimated. Measurement of trans-effects in depolarized oocytes and human embryonic kidney cells expressing hOCT2 suggests that there were different rates and specificities for cation influx and efflux. The hypothesis is raised that hOCT2 plays a physiological role in the central nervous system by regulating interstitial concentrations of monoamine neurotransmitters that have evaded high affinity uptake mechanisms. We show that amantadine does not interact with the expressed human Na+/Cl− dopamine cotransporter. However, concentrations of amantadine that are effective for the treatment of Parkinson′s disease may increase the interstitial concentrations of dopamine and other aminergic neurotransmitters by competitive inhibition of hOCT2. ER -