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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

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Summary

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 μM and 66.0 ± 2.8 pmol/min/mg protein. Dopamine was found to inhibit (R-1-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.

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Abbreviations

MAO :

monoamine oxidase

MPTP :

1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine

MPP + :

1-methyl-4-phenylpyridinium ion

1-MeDHTIQ :

1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline

1,2-DiMeDHTIQ :

1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline

1,2-DiMeDHIQ + :

1,2-dimethyl-6,7-dihydroxyisoquinolinium ion

2-MeDHIQ + :

2-methyl-6,7-dihydroxyisoquinolinium ion

TIO :

1,2,3,4-tetrahydroisoquinoline

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Author notes

  1. M. Naoi

    Present address: Department of Biosciences, Nagoya Institute of Technology, Nagoya

Authors and Affiliations

  1. Department of Food and Nutrition, Konan Women's College, Konan

    T. Takahashi

  2. Department of Applied Chemistry, Nagoya Institute of Technology, Nagoya

    Y. Deng & M. Kawai

  3. Department of Neurology, Nagoya University School of Medicine, Nagoya, Japan

    W. Maruyama

  4. Research and Development, Farmitalia Carlo Erba, Milan, Italy

    P. Dostert

Authors
  1. T. Takahashi
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  2. Y. Deng
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  3. W. Maruyama
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  4. P. Dostert
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  5. M. Kawai
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  6. M. Naoi
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Takahashi, T., Deng, Y., Maruyama, W. et al. 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 Transmission 98, 107–118 (1994). https://doi.org/10.1007/BF01277014

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  • DOI: https://doi.org/10.1007/BF01277014

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