Effect of a sulfonium analog of dopamine on the depolarization-induced release of [3H]acetylcholine from mouse striatal slices

Bethany Turowski, Michael Szkrybalo, Karen Anderson, Duane Miller, Norman Uretsky

Research output: Contribution to journalArticle

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Abstract

We have synthesized a chemical analog or dopamine in which the amino group has been replaced by a charged dimethylsulfonium group. The dopaminergic activity of this drug was evaluated by determining its ability to inhibit the depolarization-evoked release of [3H]acetylcholine from mouse striatal slices. The slices were preincubated with [3H]choline (0.1 μM) and then superfused in physiological medium. [3H]Acetylcholine release was induced by exposure of the slices to a high potassium medium (12.5 mM) for 5 min. The sulfonium analog of dopamine, dopamine, and apormorphine inhibited the evoked [3H]acetylcholine release with IC50 values of approximately 10, 2.0, and 0.3 μM respectively. The inhibition by the sulfonium analog was reversed by fluphenazine (1 μM), suggesting that the inhibition of [3H]acetylcholine release was due to the activation of dopaminergic receptors. The sulfonium analog also inhibited the uptake of [3H]dopamine into striatal slices and caused the release of exogenously taken up [3H]dopamine from these slices. The release of [3H]dopamine by the sulfonium analog was inhibited by cocaine (3 μM), suggesting that the drug-induced release of [3H]dopamine was dependent on the carrier-mediated uptake of the sulfonium analog into dopaminergic neurons. The inhibition of the evoked [3H]acetylcholine release by high concentrations (30 and 60 μM) of the sulfonium analog did not appear to be mediated by endogenous dopamine release, since the analog still inhibited [3H]acetylcholine release from slices after reserpine-α-methyl-p-tyrosine treatment, However, the inhibitory effect of the sulfonium analog at 10 μM was reduced by reserpine-α-methyl-p-tyrosine treatment, suggesting that the inhibition at lower concentrations was mediated through endogenous DA release. These results suggest that a charged compound can act as a substrate for the dopamine carrier and can activate the dopamine receptor regulating acetylcholine release. They also indicate that the nitrogen on the dopamine molecule is not essential for dopamine agonist activity.

Original languageEnglish (US)
Pages (from-to)2371-2376
Number of pages6
JournalBiochemical Pharmacology
Volume33
Issue number15
DOIs
StatePublished - Aug 1 1984
Externally publishedYes

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Corpus Striatum
Depolarization
Acetylcholine
Dopamine
Reserpine
Tyrosine
Fluphenazine
Dopamine Agents
Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Dopamine Agonists
Dopamine Receptors
Choline
Cocaine
Pharmaceutical Preparations
Inhibitory Concentration 50
Neurons
Potassium
Nitrogen
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Effect of a sulfonium analog of dopamine on the depolarization-induced release of [3H]acetylcholine from mouse striatal slices. / Turowski, Bethany; Szkrybalo, Michael; Anderson, Karen; Miller, Duane; Uretsky, Norman.

In: Biochemical Pharmacology, Vol. 33, No. 15, 01.08.1984, p. 2371-2376.

Research output: Contribution to journalArticle

Turowski, Bethany ; Szkrybalo, Michael ; Anderson, Karen ; Miller, Duane ; Uretsky, Norman. / Effect of a sulfonium analog of dopamine on the depolarization-induced release of [3H]acetylcholine from mouse striatal slices. In: Biochemical Pharmacology. 1984 ; Vol. 33, No. 15. pp. 2371-2376.
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