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

J Neural Transm Gen Sect. 1994;98(2):107-18. doi: 10.1007/BF01277014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Dopamine Plasma Membrane Transport Proteins
  • Humans
  • Isoquinolines / antagonists & inhibitors
  • Isoquinolines / pharmacokinetics*
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Neurotoxins / pharmacokinetics
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Isoquinolines
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • N-methylsalsolinium
  • Nerve Tissue Proteins
  • Neurotoxins
  • Dopamine