Uptake of the dopaminergic neurotoxin, norsalsolinol, into PC12 cells via dopamine transporter.
The uptake of norsalsolinol, a neurotoxin candidate causing parkinsonism-like symptoms, was studied in PC12 cells. The compound was actively taken up by the PC12 cells, with a Km value of 176.24 +/-9.1 microM and a maximum velocity of 55.6 +/- 7.0 pmol/min per mg protein; norsalsolinol uptake was dependent on the presence of extracellular Na+. The uptake of norsalsolinol was sensitive to two dopamine transporter inhibitors, GBR-12909 and reserpine, but was less sensitive to desipramine, a noradrenaline transporter inhibitor. Dopamine competitively inhibited norsalsolinol uptake into PC12 cells with a Ki value of 271.2 +/- 61.6 microM. These results suggest that norsalsolinol is taken up into PC12 cells mainly by the dopamine transporter.
Maruyama
Y
Y
Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Suzuki
Y
Y
Kazusaka
A
A
Fujita
S
S
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D016716:PC12 Cells; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012490:Salsoline Alkaloids / Q000378:metabolism* / Q000633:toxicity
D018759:Adrenergic Uptake Inhibitors; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D012490:Salsoline Alkaloids; D012110:Reserpine; C043425:vanoxerine; C020784:norsalsolinol; D003891:Desipramine; D004298:Dopamine