Increased site-specific phosphorylation of tyrosine hydroxylase accompanies stimulation of enzymatic activity induced by cessation of dopamine neuronal activity.

摘要: Activation of striatal dopamine (DA) neurons by neuroleptic treatment or electrical stimulation the nigrostriatal pathway increases activity tyrosine hydroxylase (TH). The increase is mediated phosphorylation enzyme. However, abolition DA neuronal [by γ-butyrolactone (GBL) transection pathway] also TH activity. Quantitative blot immunolabeling experiments using site- and state-specific antibodies to demonstrated that GBL (750 mg/kg, 35 min) significantly increased at Ser19 (+40%) Ser40 (+217%) without altering Ser31 phosphorylation. Concomitantly, [along with 3,4-dihydroxyphenylalanine (dopa) decarboxylase inhibitor NSD-1015, 100 30 min] in vivo dopa accumulation vitro 3-fold. Likewise, cerebral hemitransection (+89%) (+158%) but not Ser31; levels were accordingly (+191%). Kinetic analysis established primarily decreased Kmfor cofactor tetrahydrobiopterin (3-fold). effects abolished attenuated pretreatment agonistR-(−)-N-n-propylnorapomorphine (NPA; μg/kg, 40 min), presumably via inhibitory presynaptic autoreceptors. NPA dose-response curves for reversal GBL-induced identical; however, only highest dose reversed small variable Thus, seems be regulated both hyper- hypoactive neurons; latter case, activation caused selective Ser40.