Striatal synaptosomal dopamine synthesis

Evidence against direct regulation by an autoreceptor mechanism

David R. Compton, Kenneth M. Johnson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Regulation of the rate-limiting step in dopamine (DA) synthesis was estimated in striatal synaptosomes by measuring the rate of hydroxylation of L-4-[3H]phenylalanine, a substrate of tyrosine hydroxylase (TH). DA inhibited hydroxylation with an IC50 of 0.2 μM. The concentration-response curve of DA-induced inhibition was not affected by the presence of 1 μM chlorpromazine, a phenothiazine DA antagonist. Sulpiride and haloperidol, DA antagonists of the benzamide and butyrophenone classes respectively, also failed to alter the inhibition of substrate hydroxylation by 1 μM DA, even at cocnentrations up to 10 μM. In contrast, a parallel 15 fold shift to the right in the concentration-response curve of DA-induced inhibition of hydroxylation was obtained when 10 μM nomifensine, a competitive DA uptake inhibitor, was added. Even in the presence of nomifensine, 1μM chlorpromazine had no effect on the DA concentration-response curve. The addition of DMPH4, an artificial cofactor for TH, completely blocked DA-induced inhibition of enzymatic activity. These data suggest that direct autoreceptor control of synaptosomal TH activity does not exist in vitro, and that DA-induced inhibition of TH occurs subsequent to reuptake via classical feedback inhibition, presumably by competitive displacement of the necessary endogenous cofactor.

Original languageEnglish (US)
Pages (from-to)157-162
Number of pages6
JournalEuropean Journal of Pharmacology
Volume110
Issue number2
DOIs
StatePublished - Apr 2 1985

Fingerprint

Corpus Striatum
Autoreceptors
Dopamine
Tyrosine 3-Monooxygenase
Hydroxylation
Nomifensine
Dopamine Antagonists
Chlorpromazine
Butyrophenones
Dopamine Uptake Inhibitors
Sulpiride
Synaptosomes
Haloperidol
Phenylalanine
Inhibitory Concentration 50

Keywords

  • Autoreceptor
  • Dopamine
  • Dopamine antagonists
  • Striatum
  • Synaptosomes
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Striatal synaptosomal dopamine synthesis : Evidence against direct regulation by an autoreceptor mechanism. / Compton, David R.; Johnson, Kenneth M.

In: European Journal of Pharmacology, Vol. 110, No. 2, 02.04.1985, p. 157-162.

Research output: Contribution to journalArticle

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