The Decarboxylation of DOPA in the Parkinsonian Brain: In vivo Studies on an Animal Model

  • F. Hefti
  • E. Melamed
  • R. J. Wurtman
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 16)


The site of decarboxylation of exogenously administered L-DOPA was studied in corpora striata of rats with near-total unilateral nigrostriatal lesions. After DOPA administration, the absolute increases in dopamine (DA) levels were lower in lesioned than in unlesioned striata, suggesting that, in the intact striatum, a major part of exogenous DOPA is decarboxylated in DA neurons. DOPA can also be decarboxylated outside DA neurons, however, as shown by our finding that relatively higher DOPA decarboxylase than tyrosine hydroxylase activity or DA concentration remains in striata after the nigrostriatal lesions. Also, the percentage increases in DA formation after DOPA administration were much higher in lesioned than in control striata. Rats with both raphé and nigrostriatal lesions failed to exhibit further reductions in striatal DOPA decarboxylase activity or diminished biochemical or behavioral (turning behavior) reactions to DOPA. Inhibition of the DOPA decarboxylase contained in brain capillary endothelial cells did not abolish DA formation in lesioned striata or circling behavior after DOPA administration. These findings all suggest an additional cell type in the striatum as the site of DOPA’s decarboxylation in the absence of DA neurons.


Tyrosine Hydroxylase Kainic Acid Medial Forebrain Bundle Lesion Side Brain Capillary Endothelial Cell 
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  1. Bertler. A, Falck, B., Owman. C., Rosengren, E.: The localization of monoaminergic blood-brain barrier mechanisms. Pharmacol. Rev. 18 369–385 (1966).Google Scholar
  2. Duvoisin, R. C., Mytilineou, C. : Where is L-DOPA decarboxylated after 6-hydroxydopamine nigrotomy? Brain Res. 152 369–373 (1978).CrossRefGoogle Scholar
  3. Neurology.
    Fahrt,.S, Calne, M.L: Considerations in the management of parkinsonism.Neuruology28, 5–7 (1978).Google Scholar
  4. Feiice, L.J., Feiice, J. D., Kissinger, P. T. Determination of catecholamines in rat brain parts by reverse-phase ion-pair liquid chromatography. J. Neurochem. 31 1461–1466 (1978).CrossRefGoogle Scholar
  5. Hefti, F: A simple, sensitive method for measuring 3, 4-dihydroxyphenyl acetic acid and homovanillic acid in rat brain tissue using high performance liquid chromatography with electrochemical detection. Life Sci. 25 775–782 (1979).PubMedCrossRefGoogle Scholar
  6. Hornykiewicz, O: The mechanism of action of L-DOPA in Parkinson’s disease. Life Sci. 15 1249–1259 (1974).PubMedCrossRefGoogle Scholar
  7. Langelier, F., Roberge, A. G., Boucher, R., Poirier, L.J. : Effects of chronically administered L-DOPA in normal and lesioned cats. J. Pharmacol. Exp. Ther. 187 15–26 (1973).PubMedGoogle Scholar
  8. Lytle, L. D., Hurko, O., Romero, J. A., Cottman, K., Leehey, D., Wurt- man, R. J.: The effects of 6-hydroxydopamine pretreatment on the accumulation of DOPA and dopamine in brain and peripheral Organs following L-DOPA administration. J. Neural Transm. 33 63–72 (1972).PubMedCrossRefGoogle Scholar
  9. McGeer, E. G., Fibiger, H. C., McGeer, P. L., Brooke, S: Temporal changes in amine synthesizing enzymes of rat extrapyramidal struetures after hemitranssections or 6-OHDA administration. Brain Res. 52 289–300 (1973).CrossRefGoogle Scholar
  10. Melamed, E., Hefti, F., Wurtman, R. J: Decarboxylation of L-DOPA in Parkinson’s disease. Is there a role for serotoninergic neurons? Submitted for publication.Google Scholar
  11. Ng, L.K.Y., Chase, T.N., Colburn, R.W., Kopin, I. J : L-DOPA in Parkinsonism; a possible mechanism of action. Neurology 22, 688–695 (1972).PubMedGoogle Scholar
  12. Schwarcz, R., Coyle, J. T: Striatal lesions with kainic acid; neurochemical characteristics. Brain Res. 127 235–250 (1977).CrossRefGoogle Scholar
  13. Ungerstedt, U: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of nigrostriatal dopamine system. Acta Physiol. Scand., suppl. 367 69–93 (1971).Google Scholar
  14. Vogt, M: Drug-induced changes in brain dopamine and their relation to parkinsonism. Sci. Basis Med. Annu. Rev., chapter XVI, pp. 276–291 (1970).Google Scholar
  15. Waymire, J. C., Bujn, R., Weiner, N: Assay of tyrosine hydroxylase by coupled decarboxylation of dopa formed from l-14C-tyrosine. Anal. Biochem. 43 588–600 (1971).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • F. Hefti
    • 1
  • E. Melamed
    • 1
  • R. J. Wurtman
    • 1
    • 2
  1. 1.Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food ScienceMassachusetts Institute TechnologyCambridgeUSA
  2. 2.Laboratory of Neuroendocrine RegulationMassachusetts Institute of TechnologyCambridgeUSA

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