Peripherally administered (6R)-tetrahydrobiopterin increases in vivo tyrosine hydroxylase activity in the striatum measured by microdialysis both in normal mice and in transgenic mice carrying human tyrosine hydroxylase

Neurosci Lett. 1994 Nov 21;182(1):44-6. doi: 10.1016/0304-3940(94)90201-1.

Abstract

The intraperitoneal administration of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), the natural cofactor of tyrosine hydroxylase (TH), increased the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) measured using microdialysis under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 (in vivo TH activity) in the striatum both of transgenic mice carrying human TH gene and of non-transgenic mice, to a similar extent by about 4-fold. The results indicate that the peripherally administered 6R-BH4 activates in vivo TH activity in the nigrostriatal dopamine neurons in both non-transgenic and transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Biopterins / analogs & derivatives*
  • Biopterins / pharmacology
  • Corpus Striatum / enzymology*
  • Dihydroxyphenylalanine / metabolism
  • Humans
  • Hydrazines / pharmacology
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics*
  • Mice, Transgenic / metabolism*
  • Microdialysis
  • Reference Values
  • Tyrosine 3-Monooxygenase / genetics*
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Hydrazines
  • Biopterins
  • Dihydroxyphenylalanine
  • 3-hydroxybenzylhydrazine
  • Tyrosine 3-Monooxygenase
  • sapropterin