Reversal of alpha-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, alpha-methyltyrosine (alpha-MT). A subcutaneous dose of 250 mg/kg of alpha-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 alpha-MT-treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by alpha-MT in mice. We suggest that the reversal of the alpha-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system.
Hirotsu
I
I
Laboratory of Experimental Pharmacology, Suntory Institute for Biomedical Research, Osaka, Japan.
Horikawa
Y
Y
Kihara
T
T
Ishihara
T
T
Kanai
T
T
D000818:Animals; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000032:analysis; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D001708:Biopterins; D019805:alpha-Methyltyrosine; C003402:sapropterin; D004298:Dopamine; D009638:Norepinephrine