Release of dopamine via the human transporter

Amy J. Eshleman, Robert A. Henningsen, Kim Neve, Aaron Janowsky

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage and release mechanisms. Cells expressing the dopamine transporter acquired the capacity to take up and release dopamine via the transporter. Ionic conditions that stimulate inside- out transport in vivo, such as depolarizing concentrations of K+ or low concentrations of extracellular Na+, were found to stimulate Ca2+- independent release of [3H]dopamine from transfected COS-7 cells. Dopamine uptake inhibitors had one of three effects on transporter-mediated efflux. Some drugs, in addition to inhibiting uptake, inhibited spontaneous release of dopamine. Drugs in this class included mazindol, GBR-12935, bupropion, nomifersine, and benztropine. All of the drugs with the potential for abuse by humans either enhanced release (methamphetamine, amphetamine, and ethanol) or had no effect on release (phencyclidine, cocaine, and WIN 35,428). The ability to define classes of uptake blockers based on their effects on human transporter mediated dopamine efflux may lead to the identification of structural features of the transporter that differentiate abused from nonabused drugs.

Original languageEnglish (US)
Pages (from-to)312-316
Number of pages5
JournalMolecular Pharmacology
Volume45
Issue number2
StatePublished - Feb 1994

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Dopamine Plasma Membrane Transport Proteins
Dopamine
COS Cells
Pharmaceutical Preparations
Benztropine
Mazindol
Dopamine Uptake Inhibitors
Bupropion
Phencyclidine
Methamphetamine
Amphetamine
Cocaine
Ethanol
Complementary DNA
Cell Line

ASJC Scopus subject areas

  • Pharmacology

Cite this

Eshleman, A. J., Henningsen, R. A., Neve, K., & Janowsky, A. (1994). Release of dopamine via the human transporter. Molecular Pharmacology, 45(2), 312-316.

Release of dopamine via the human transporter. / Eshleman, Amy J.; Henningsen, Robert A.; Neve, Kim; Janowsky, Aaron.

In: Molecular Pharmacology, Vol. 45, No. 2, 02.1994, p. 312-316.

Research output: Contribution to journalArticle

Eshleman, AJ, Henningsen, RA, Neve, K & Janowsky, A 1994, 'Release of dopamine via the human transporter', Molecular Pharmacology, vol. 45, no. 2, pp. 312-316.
Eshleman, Amy J. ; Henningsen, Robert A. ; Neve, Kim ; Janowsky, Aaron. / Release of dopamine via the human transporter. In: Molecular Pharmacology. 1994 ; Vol. 45, No. 2. pp. 312-316.
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