N-methyl-4-phenylpyridinium and an endogenously formed analog, N-methylated beta-carbolinium, inhibit striatal tyrosine hydroxylation in freely moving rats.
The effects of N-methyl-4-phenylpyridinium (MPP+) and its endogenous analog, 2,9-di-methyl-norharmanium (2,9-Me2NH+), on in vivo tyrosine hydroxylation were evaluated in freely moving rats. MPP+ gradually but almost completely reduced tyrosine hydroxylation, even at a dose as low as 0.05 mM. This effect was considered to be caused by the inhibition of tyrosine hydroxylase (TH) activation. On the contrary, 1 mM 2,9-Me2NH+ rapidly reduced 3,4-dihydroxyphenylalanine production to 10% of the basal level only during its perfusion, indicating direct inhibition of TH activity. The present study revealed that MPP+ and 2,9-Me2NH+ were taken up into dopaminergic neurons and then inhibited in vivo dopamine synthesis prior to cell death possibly in different manners.
Matsubara
K
K
Department of Legal Medicine, Shimane Medical University, Izumo, Japan.
Idzu
T
T
Kobayashi
Y
Y
Nakahara
D
D
Maruyama
W
W
Kobayashi
S
S
Kimura
K
K
Naoi
M
M
D015655:1-Methyl-4-phenylpyridinium / Q000031:analogs & derivatives / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects*
D002243:Carbolines; C005986:2,9-dimethyl-beta-carbolinium; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium