Presynaptic Dopamine Autoreceptors Control Tyrosine Hydroxylase Activation in Depolarized Striatal Dopaminergic Terminals

摘要: : The possible control of tyrosine hydroxylase (TH) activity by dopaminergic receptor-dependent mechanisms was investigated using rat striatal slices or synaptosomes incubated in the presence various 3,4-dihydroxyphenylethylamine (dopamine DA) agonists and antagonists. Under “normal” conditions (4.8 mM K+ incubating medium), DA apomorphine, 6,7-dihydroxy-N, N-dimethyl-2-aminotetralin (TL-99), 7-hydroxy-N, N-dipropyl-2-aminotetralin (7-OH-DPAT), trans- (–)-4,4a,5,6,7,8,8a,9-octahydro- 5 -propyl-2H-pyrazolo-3,4-quinoline, 3-(3-hydroxyphenyl)-N-n-propylpiperidine decreased TH soluble extracts tissues. In case catechol-containing drugs apomorphine TL-99, this effect partly due to a direct inhibition enzyme, but all other cases it appeared depend on stimulation presynaptic autoreceptors. No antagonists detected under conditions. contrast, when tissues were K+-enriched (60 mM) medium, (–)-sulpiride enhanced activation depolarization whereas ineffective. Because also increased enzyme exposed inducing release DA, such as veratridine d-amphetamine, is concluded that stimulating antagonist resulted fact from blockade negative normally triggered endogenous acting contrast K+-induced depolarization, evoked tissue incubation with dibutyryl cyclic AMP unaffected typical agonist 7-OH-DPAT (–)-sulpiride. This would suggest via autoreceptors concerns modulations AMP-dependent phosphorylation enzyme.