I  U  P  A  C






News & Notices

Organizations & People

Standing Committees

Divisions

Projects

Reports

Publications
..CI
..PAC
..Macro. Symp.

..Books
..Solubility Data

Symposia

AMP

Links of Interest

Search the Site

Home Page

 

Pure Appl. Chem. Vol. 72, No. 6, pp. 1045-1050, 2000


The mechanism of the releasing action of amphetamine. Uptake, superfusion, and electrophysiological studies on transporter-transfected cells*

C. Pifl1**, H. H Sitte1, H. Reither1, and E. A. Singer2

1Institute of Biochemical Pharmacology;
2
Pharmacological Institute, University of Vienna, A-1090 Vienna, Austria

Abstract: Amphetamine analogues are able to induce signs of neurotoxicity in the brain. In order to understand this type of neurotoxicity, the interaction of amphetamine with its molecular targets must be elucidated. These molecular targets are plasmalemmal and vesicular monoamine transporters. We investigated the interaction of amphetamine with these transporters in cells transfected with the respective cDNA. Superfusion and whole-cell, patch-clamp experiments were performed, and the toxicity of substrates of the transporters was studied. Amphetamine was taken up by dopamine transporter-expressing cells in a sodium-dependent and cocaine-blockable manner. Furthermore, it elicited inward currents in these cells concentration-dependently. Correlation of uptake, release, and patch-clamp experiments suggest that ion fluxes induced by substrate-gating on transporters may significantly contribute to the releasing action of amphetamine and of other transporter substrates. Dopamine accumulation into serotoninergic terminals depleted of serotonin by 3,4-methylenedioxymethamphetamine was discussed as a mechanism of Ecstasy-toxicity. This is in agreement with a toxic effect of intracellular dopamine which could be demonstrated on our transporter-overexpressing cells. These results, apart from their relevance for the toxicity by amphetamine analogues, may also have bearings on the mechanisms in neurodegenerative diseases affecting monoamine transmitters.

*Lectures presented at the 4th Congress of Toxicology in Developing Countries (4th CTOX-DC), Antalya, Turkey, 6-10 November 1999
**Corresponding author

Back to Contents for access to full text

 


Page last modified 13 September 2000.
Copyright © 2000 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact web manager.