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Relationship between TIQs and Parkinson’s disease

  • S. Ohta
  • M. Kohno
  • Y. Makino
  • O. Tachikawa
  • Y. Tasaki
  • K. Kikuchi
  • M. Hirobe
Conference paper
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

1,2,3,4-Tetrahydroisoquinoline (TIQ) has been assumed to be one of the endogenous substances inducing Parkinson’s disease because of its structural similarity to 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Actually TIQ and its related compound, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were coexistent as endogenous amines in rat brain and human brain. lMeTIQ content was markedly reduced in the parkinsonian brain particularly in the frontal lobe. The 1MeTIQ content also decreased with aging.

TIQs were present in foods, such as wine, cocoa, cheese, milk, egg and banana. In addition, TIQs could penetrate the blood-brain barrier, and hence TIQ from foods may accumulate in the brain over long periods.

Metabolism of TIQ was investigated in connection with metabolism of debrisoquine which is a common marker for the metabolism in human. The main metabolite of TIQ was 4-hydroxy-TIQ. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson’s disease.

Keywords

Parkinsonian Brain Brain Accumulation Endogenous Amine Cycad Seed Chronic Parkinsonism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Barbeau A, Cloutier T, Roy M, Plasse L, Paris S, Poirier J (1985) Ecogenetics of Parkinson’s disease: 4-hydroxylation of debrisoquine. Lancet ii: 1213–1216Google Scholar
  2. Gonzalez FJ, Matsunaga T, Nagata K, Meyer UA, Nebert DW, Pastewka J, Kozak CA, Gillette J, Gelboin HV, Hardwick JP (1987) Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily, regulation, chromosomal mapping, and molecular analysis of the DA rat polymorphism. DNA 6: 149–161PubMedCrossRefGoogle Scholar
  3. Kikuchi K, Nagatsu Y, Makino Y, Mashino T, Ohta S, Hirobe M (1991) Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds: 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1 -methyl-1,2,3,4-tetrahydroisoquinoline (1 MeTIQ). Drug Metab Dispos 19: 257–262PubMedGoogle Scholar
  4. Kohno M, Ohta S, Hirobe M (1986) Tetrahydroisoquinoline and 1-methyltetrahy- droisoquinoline as novel endogenous amines in rat brain. Biochem Biophys Res Commun 140: 448–454PubMedCrossRefGoogle Scholar
  5. Langston JW, Ballard P, Tetrad JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979–980PubMedCrossRefGoogle Scholar
  6. Lasala JM, Coscia CJ (1979) Accumulation of a tetrahydroisoquinoline in phenylketonuria. Science 203: 283–284PubMedCrossRefGoogle Scholar
  7. Makino Y, Ohta S, Tachikawa O, Hirobe M (1988) Presence of tetrahydroisoquinoline and 1-methyltetrahydroisoquinoline in foods: compounds related to Parkinson’s disease. Life Sci 43: 373–378PubMedCrossRefGoogle Scholar
  8. Nagatsu T, Yoshida M (1988) An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. Neurosci Lett 87: 178–182PubMedCrossRefGoogle Scholar
  9. Nesterick CA, Rahwan RG (1979) Detection of endogenous salsolinol in neonatal rat tissue by a radioenzymatic-thin-layer chromatographic assay. J Chromatogr Biomed Appi 164: 205–216CrossRefGoogle Scholar
  10. Niwa T, Takeda N, Kaneda N, Hashizume Y, Nagatsu T (1987) Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in parkinsonian and normal human brains. Biochem Biophys Res Commun 144: 1084–1089PubMedCrossRefGoogle Scholar
  11. Niwa T, Yoshizumi H, Tatematsu A, Matsuura S, Nagatsu T (1989) Presence of tetrahydroisoquinoline, a parkinsonism-related compound, in foods. J Chromatogr Biomed Appi 493: 347–352CrossRefGoogle Scholar
  12. Ohta S, Kohno M, Makino Y, Tachikawa O, Hirobe M (1987) Tetrahydroisoquinoline and 1-methyltetrahydroisoquinoline are present in the human brain: relation to Parkinson’s disease. Biomed Res 8: 453–456Google Scholar
  13. Ohta S, Tachikawa O, Makino Y, Tasaki Y, Hirobe M (1990) Metabolism and brain accumulation of tetrahydroisoquinoline ( TIQ), a possible parkinsonism-inducing substance, in an animal model of a poor debrisoquine metabolizer. Life Sci 46: 599–605Google Scholar
  14. Sandler M, Carter SB, Hunter KR, Stern GM (1973) Tetrahydroisoquinoline alkaloids: in vivo metabolites of L-dopa in man. Nature 241: 439–443PubMedCrossRefGoogle Scholar
  15. Spencer PS, Roy DN, Ludolph A, Hugon J, Dwivedi MP, Schaumburg HH (1986) Lathyrism: evidence for role of the neuroexcitatory amino acid BOAA. Lancet ii: 1066–1067Google Scholar
  16. Spencer PS, Nunn PB, Hugon J, Ludolph AC, Ross SM, Roy DN, Robertson RC (1987) Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 237: 517–522PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1991

Authors and Affiliations

  • S. Ohta
    • 1
  • M. Kohno
    • 1
  • Y. Makino
    • 1
  • O. Tachikawa
    • 1
  • Y. Tasaki
    • 1
  • K. Kikuchi
    • 1
  • M. Hirobe
    • 1
  1. 1.Faculty of Pharmaceutical SciencesUniversity of TokyoHongo, Bunkyo-ku, Tokyo 113Japan

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