Catecholamine transport by the organic cation transporter type 1 (OCT1).

Article Details

Citation

Copy to clipboard

Breidert T, Spitzenberger F, Grundemann D, Schomig E

Catecholamine transport by the organic cation transporter type 1 (OCT1).

Br J Pharmacol. 1998 Sep;125(1):218-24.

PubMed ID

9776363 [ View in PubMed

]

Abstract

1. Liver and kidney extract adrenaline and noradrenaline from the circulation by a mechanism which does not seem to be one of the classical catecholamine transporters. The hypothesis that OCT1 is involved the organic cation transporter type 1 which exists in rat kidney and liver-was tested. 2. Based on human embryonic kidney cells (293), we constructed a cell line which stably expresses OCT1r (293OCT1r cells). Transfection with OCT1 resulted in a transport activity not only for prototypical known substrates of OCT1 such as 3H-1-methyl-4-phenylpyridinium and 14C-tetraethylammonium but also for the catecholamines 3H-adrenaline, 3H-noradrenaline (3H-NA) and 3H-dopamine (3H-DA), the indoleamine 3H-5-hydroxytryptamine (3H-5HT) as well as the indirect sympathomimetic 14C-tyramine. 3. For 3H-DA, 3H-5HT and 3H-NA, at non-saturating concentrations, the rate constants for inwardly directed substrate flux (kin) were 6.9+/-0.8, 3.1+/-0.2, and 1.2+/-0.1 microl min(-1) mg protein(-1). In wild type cells (293WT) the corresponding kin's were considerably lower, being 0.94+/-0.40, 0.47+/-0.08 and 0.23+/-0.05 microl min(-1) mg protein ' (n=12). The indirectly determined half-saturating concentrations of DA, 5HT, and NA were 1.1 (95% c.i.: 0.8, 1.4), 0.65 (0.49, 0.86), and 2.8 (2.1, 3.7) mmol l(-1) (n=3). 4. Specific 3H-DA uptake in 293OCT1r cells was resistant to cocaine (1 micromoll(-1)), 3H-5HT uptake was resistant to citalopram (300 nmol l(-1)) and 3H-NA uptake was resistant to desipramine (100 nmoll(-1)), corticosterone (1 micromol l(-1)), and reserpine (10 nmoll(-1)) which rules out the involvement of classical transporters for biogenic amines. 5. The findings demonstrate that OCTI efficiently transports catecholamines and other biogenic amines and support the hypothesis that OCT1 is responsible for hepatic and renal inactivation of circulating catecholamines.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Dopamine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate	Details
Epinephrine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate	Details
Norepinephrine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate	Details
Reserpine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Inhibitor	Details