Reversal of α-Methyltyrosine-Induced Hypoactivity by 6-(R)-5,6,7,8-Tetrahydro-L-Erythrobiopterin (R-THBP) in Mice

The effects of peripheral administration of 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, α-methyltyrosine (α-MT). A subcutaneo...

Full description

Saved in:
Bibliographic Details
Published inJapanese journal of pharmacology Vol. 58; no. 1; pp. 67 - 73
Main Authors Hirotsu, Ichiro, Horikawa, Yoshiko, Kihara, Tetsuro, Ishihara, Takafumi, Kanai, Tadashi
Format Journal Article
LanguageEnglish
Published Kyoto Japanese Pharmacological Society 1992
Subjects
alpha-Methyltyrosine
Animals
Biochemistry and metabolism
Biological and medical sciences
Biopterins - administration & dosage
Biopterins - analogs & derivatives
Biopterins - pharmacology
Brain - drug effects
Brain Chemistry - drug effects
Central nervous system
Dopamine - analysis
Fundamental and applied biological sciences. Psychology
Locomotion - drug effects
Male
Methyltyrosines - pharmacology
Mice
Mice, Inbred Strains
Norepinephrine - analysis
Vertebrates: nervous system and sense organs
Enzyme
Rodentia
Central nervous system
Metabolism
Tyrosine 3-monooxygenase
Cofactor
Locomotion
Vertebrata
Mammalia
Mouse
Tetrahydrobiopterin
Biogenic amine
Brain (vertebrata)
Online AccessGet full text

Cover

More Information
Summary:The effects of peripheral administration of 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, α-methyltyrosine (α-MT). A subcutaneous dose of 250 mg/kg of α-MT decreased markedly both ambulatory activity and cerebral contents of norepinephrine, dopamine and their metabolites in mice. An intraperitoneal dose of 100 mg/kg of R-THBP, which did not alter ambulatory activities in normal mice, improved the hypoactivity in α-MT-treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by α-MT in mice. We suggest that the reversal of the α-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0021-5198
1347-3506
DOI:10.1016/S0021-5198(19)39779-3