Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by σ2 receptor agonists and antagonists

Sari E Izenwasser, DeDeene Thompson-Montgomery, Sophia E. Deben, Iffat N. Chowdhury, Linda L. Werling

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Some σ receptor ligands have been shown to bind with low affinity to the dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously been shown whether any of these compounds influence release of dopamine via facilitated exchange diffusion. To further examine the nature of the interaction between σ receptor ligands and the dopamine transporter, the effects of σ receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated [3H]dopamine release at concentrations consistent with their affinities for σ2 receptors. In contrast, BD737 (1S,2R-(-)-cis-N-{2-(3,4-dichlorophenyl)ethyl}-N-methyl-2-(1- pyrrolidinyl)cyclohexylamine), a σ1 receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer of pentazocine alone had any effect on basal [3H]dopamine release under these conditions. Three antagonists at σ receptors, one of which is non-selective for subtypes, and two of which are σ2-selective, all blocked the enhancement of stimulated release produced by (+)-pentazocine. Enhancement of stimulated release by (- )-pentazocine was similarly blocked by σ2 receptor antagonists. Our data support the contention that it is possible to regulate transporter-mediated events with drugs that act at a subpopulation of σ receptors pharmacologically identified as the σ2 subtype.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalEuropean Journal of Pharmacology
Volume346
Issue number2-3
DOIs
StatePublished - Apr 10 1998
Externally publishedYes

Fingerprint

Pentazocine
Dopamine Plasma Membrane Transport Proteins
Amphetamine
Dopamine
Ligands
Facilitated Diffusion
Dopamine Agents
Putamen
In Vitro Techniques
Pharmaceutical Preparations

Keywords

  • Caudate putamen
  • Cocaine
  • Dopamine transporter
  • Dopamine uptake

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by σ2 receptor agonists and antagonists. / Izenwasser, Sari E; Thompson-Montgomery, DeDeene; Deben, Sophia E.; Chowdhury, Iffat N.; Werling, Linda L.

In: European Journal of Pharmacology, Vol. 346, No. 2-3, 10.04.1998, p. 189-196.

Research output: Contribution to journalArticle

Izenwasser, Sari E ; Thompson-Montgomery, DeDeene ; Deben, Sophia E. ; Chowdhury, Iffat N. ; Werling, Linda L. / Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by σ2 receptor agonists and antagonists. In: European Journal of Pharmacology. 1998 ; Vol. 346, No. 2-3. pp. 189-196.
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