Human Neurons Express the Polyspecific Cation Transporter hOCT2, Which Translocates Monoamine Neurotransmitters, Amantadine, and Memantine

• DOI: 10.1124/mol.54.2.342
• Publication Date: 2018-01-08T20:31:02Z
• Authors: Andreas E. Busch; Ulrich Karbach; Dagmar Miska; Valentin Gorboulev; Aida Akhoundova; Christopher Volk; Petra Arndt; Jochen C. Ulzheimer; Mark S. Sonders; Carmen Baumann; Siegfried Waldegger; Florian Lang; Hermann Koepsell
• Keywords: Amantadine; Memantine

Recently, we cloned the human cation transporter hOCT2, a member of new family polyspecific transporters from kidney, and demonstrated electrogenic uptake tetraethylammonium, choline, N¹-methylnicotinamide, 1-methyl-4-phenylpyridinium. Using polymerase chain reaction amplification, cDNA sequencing,<i>in situ</i> hybridization, immunohistochemistry, now show that hOCT2 message protein are expressed in neurons cerebral cortex various subcortical nuclei. In <i>Xenopus laevis</i> oocytes expressing transport norepinephrine, histamine, dopamine, serotonin, antiparkinsonian drugs memantine amantadine was by tracer influx, efflux, electrical measurements, or combination. Apparent <i>K</i>_<i>m</i> values 1.9 ± 0.6 mm (norepinephrine), 1.3 0.3 (histamine), 0.39 0.16 (dopamine), 80 20 μm(serotonin), 34 5 μm (memantine), 27 3 (amantadine) were estimated. Measurement <i>trans</i>-effects depolarized embryonic kidney cells suggests there different rates specificities for influx efflux. The hypothesis is raised plays physiological role central nervous system regulating interstitial concentrations monoamine neurotransmitters have evaded high affinity mechanisms. We does not interact with Na⁺/Cl⁻ dopamine cotransporter. However, effective treatment Parkinson′s disease may increase other aminergic competitive inhibition hOCT2.