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Human Nigrostriatal Dopamine Neurons Express Low Levels of GTP Cyclohydrolase I mRNA

  • Kei Hirayama
  • Gregory Kapatos

Abstract

GTP cyclohydrolase I (GTPCH; EC 3.5.4.16) is the first and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4) (1). BH4 is the required cofactor for the family of aromatic amino acid monoxygenases that includes tyrosine hydroxylase, tryptophan hydroxylase, and phenylalanine hydroxylase (2). BH4 is also essential for activity of the nitric oxide synthases (3,4). Monoamine and nitric oxide synthesis are therefore influenced by BH4 availability. GTPCH expression in human (5), rat (6, 7, 8, 9) and mouse (10,11) brain has been localized at the cellular level to monoamine-secreting neurons. GTPCH mRNA abundance in rat and mouse brain (7, 11) and GTPCH protein content in rat brain (9) are heterogeneous across different population of monoaminergic neurons, with low levels found within nigrostriatal dopamine neurons and high levels within the serotonin neurons of the dorsal raphe.

Keywords

Locus Coeruleus Dorsal Raphe Phenylalanine Hydroxylase Serotonin Neuron Nigrostriatal Dopaminergic Neuron 
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. 1.
    Nichol C.A., Smith G.K., and Duch D.S. Biosynthesis and metabolism of tetrahydrobiopterin and molybdopterin. Annu. Rev. Biochem. 54, 729–764, 1985PubMedCrossRefGoogle Scholar
  2. 2.
    Kaufman S. “Properties of the pterin-dependnt aromatic amino acid hydoxylases.” In CIBA foundation symposium, Vol. 22 Aromatic amino acids in the brain, pp 85–115. Amsterdam, Elsevier, 1974Google Scholar
  3. 3.
    Kwon, N.S., Nathan, C.F., and Stuehr, D.J. Reduced biopterin as a cofactor in the generation of nitrogen-oxide by murine macrophages. J. Biol. Chem. 264, 20496–20501, 1989PubMedGoogle Scholar
  4. 4.
    Tayeh, M.A., and Marleta, M.A. Macrophage oxidation of L-arginine to nitric-oxide, nitrite, and nitrate- tetrahydrobiopterin is required as a cofactor. J. Biol. Chem. 264, 19654–19685, 1989PubMedGoogle Scholar
  5. 5.
    Nagatsu I., Ikemoto K., Kitahama K., Nishimura A., Ichinose H., and Nagatsu T. Specific localization of the guanosine triphosphate (GTP) cyclohydrolase immunoreactivity in the human brain. J. Neural Transm. 106, 607–617, 1999PubMedCrossRefGoogle Scholar
  6. 6.
    Hirayama K., Lentz S.I., and Kapatos G. Tetrahydrobiopterin cofactor biosynthesis; GTP cyclohydrolase I mRNA expression in rat brain and superior cervical ganglia. J. Neurochem. 61, 1006–1014, 1993PubMedCrossRefGoogle Scholar
  7. 7.
    Lentz S. I., and Kapatos G. Tetrahydrobiopterin biosynthesis in the rat brain heterogeneity of GTP cyclohydrolase I mRNA expression in monoamine-containing neurons. Neurochem. Int. 28, 569–582, 1996PubMedCrossRefGoogle Scholar
  8. 8.
    Dassesse D., Hemmens B., Cuvelier L., and Resibois A. GTP cyclohydrolase-I like immunoreactivity in rat brain. Brain Res, 777, 187–201, 1997PubMedCrossRefGoogle Scholar
  9. 9.
    Hirayama K., and Kapatos G. Nigrostriatal dopamine neuron express low levels of GTP cyclohydrolase I protein. J. Neurochem. 70, 164–170, 1998PubMedCrossRefGoogle Scholar
  10. 10.
    Nagatsu I., Ichinose H., Sakai M., Titani K., Suzuki M., and Nagatsu T. Immunocytochemical localization of GTP cyclohydrolase I in the brain, adrenal gland, and liver of mice J. Neural Transm. 102, 175–188, 1995CrossRefGoogle Scholar
  11. 11.
    Shimoji M., Hirayama, K., Hyland K., and Kapatos G. GTP cyclohydrolase I gene expression in the brains of male and female hph-1 mice. J. Neurochem. 72, 757–764, 1999PubMedCrossRefGoogle Scholar
  12. 12.
    Ichinose H., Ohye T., Takahashi E., Seki N., Hori T., Segawa M., Nomura Y., Endo K., Tanaka H., Tsuji S., Fujita K., and Nagatsu T. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nature Genetics, 8, 236–241, 1994PubMedCrossRefGoogle Scholar
  13. 13.
    Rajput A.H., Gibb W.R.G., Zhong X.H., Shannak K.S., Kish S., Chang L.G., and Hornykiewicz O. Dopa-responsive dystonia pathological and biochemical observations in a case. Ann. Neurol. 35, 396–402, 1994PubMedCrossRefGoogle Scholar
  14. 14.
    Furukawa Y., Mizuno Y., Nishi K., and Narabayashi H. A clue to the pathogenesis of Doparesponsive dystonia. Ann. Neurol. 37, 139–140, 1995PubMedCrossRefGoogle Scholar
  15. 15.
    Furukawa Y., Nishi K., Kondo T., Tanabe K, Mizuno Y Significance of CSF total neopterin and biopterin in inflammatory neurological diseases. J. Neurol. Sci. 111, 65–72, 1989CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Kei Hirayama
    • 1
    • 2
  • Gregory Kapatos
    • 1
    • 2
  1. 1.Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral NeurosciencesWayne State University School of MedicineDetroitUSA
  2. 2.Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitUSA

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