Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine.

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Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H

Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine.

Mol Pharmacol. 1998 Aug;54(2):342-52.

PubMed ID

9687576 [ View in PubMed

]

Abstract

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 Km values of 1.9 +/- 0.6 mM (norepinephrine), 1.3 +/- 0.3 mM (histamine), 0.39 +/- 0.16 mM (dopamine), 80 +/- 20 microM (serotonin), 34 +/- 5 microM (memantine), and 27 +/- 3 microM (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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Amantadine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Substrate Inhibitor	Details
Dopamine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Substrate Inhibitor	Details
Histamine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Substrate Inhibitor	Details
Memantine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Substrate	Details
Norepinephrine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Substrate Inhibitor	Details

Polypeptides

Name	UniProt ID
Solute carrier family 22 member 2	O15244	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Amantadine	Solute carrier family 22 member 2	IC 50 (nM)	23000	N/A	N/A	Details