Uptake of a neurotoxin-candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine transport system.
Uptake of catechol isoquinolines to dopamine cells was studied using human dopaminergic neuroblastoma SH-SY5Y cells. Only (R)-1,2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-1,2-DiMeDHTIQ] was transported by dopamine uptake system, while (S)-1,2-DiMeDHTIQ, (R)- and (S)-1-methyl-6,7-dihydroxy-tetrahydroisoquinoline, and 1,2-dimethyl-6,7-dihydroxyisoquinolinum ion were not. Kinetical study showed that the uptake of (R)-1,2-DiMeDHTIQ followed the Michaelis-Menten equation, and the values of the Michaelis constant and the maximal velocity were obtained to be 102.6 +/- 36.9 microM and 66.0 +/- 2.8 pmol/min/mg protein. Dopamine was found to inhibit (R)-1,2-DiMeDHTIQ uptake competitively. These results suggest that the selective uptake by dopamine transporter may account for the specific neurotoxicity of (R)-1,2-DiMeDHTIQ to dopamine neurons.
Takahashi
T
T
Department of Food and Nutrition, Konan Women's College, Japan.
Deng
Y
Y
Maruyama
W
W
Dostert
P
P
Kawai
M
M
Naoi
M
M
D002352:Carrier Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C089303:N-methylsalsolinium; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D004298:Dopamine