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.
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.
Nagatsu
T
T
Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Nakahara
D
D
Kobayashi
K
K
Morita
S
S
Sawada
H
H
Mizuguchi
T
T
Kiuchi
K
K
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism*; D017551:Microdialysis; D012016:Reference Values; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D001708:Biopterins; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase; C003402:sapropterin