Inactivation of tyrosine hydroxylase in rat striatum by 1-methyl-4-phenylpyridinium ion (MPP+).

We report that 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inactivated tyrosine hydroxylase (TH) when MPP+ was directly infused into the striatum. We examined both in vitro TH activity and TH content measured by an enzyme immunoassay in the rat striatum after MPP+ was administered by an in vivo brain microdialysis probe. MPP+ caused the inhibition of TH activity but did not influence TH content in the ipsilateral striatum. These results indicate that MPP+ may cause an acute inactivation of TH after continuous exposure at the high concentrations.