This article is part of the supplement: 17th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access Meeting abstract

Amphetamine actions rely on the availability of phosphatidylinositol-4,5-bisphosphate

Florian Buchmayer1, Klaus Schicker1, Gerald Stübiger1, Peter J Hamilton2, Petra Geier1, Andreas Jurik3, René Weissensteiner3, Thomas Steinkellner1, Heinrich J Matthies2, Therese Montgomery1, Marie-Therese Winkler1, Jae-Won Yang1, Marion Holy1, Gerhard F Ecker3, Aurelio Galli2, Valery Bochkov1, Stefan Boehm1 and Harald H Sitte1*

Author Affiliations

1 Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria

2 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA

3 Department of Medicinal Chemistry, University of Vienna, 1090 Vienna, Austria

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BMC Pharmacology 2011, 11(Suppl 2):A19  doi:10.1186/1471-2210-11-S2-A19

The electronic version of this article is the complete one and can be found online at:

Published:5 September 2011

© 2011 Buchmayer et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Neuronal functions, such as excitability or endo- and exocytosis, require phosphatidylinositol-4,5-bisphosphate (PIP2) since ion channels and other proteins involved in these processes are regulated by PIP2. Monoamine transporters control neurotransmission by removing monoamines from the extracellular space. They also display channel properties, but their regulation by PIP2 has not been reported. The psychostimulant amphetamine acts on monoamine transporters to stimulate transportermediated currents and efflux and thereby increases the levels of extracellular monoamines.

Methods and results

Direct or receptor-mediated activation of phospholipase C (PLC) reduced membrane PIP2 and amphetamine-evoked currents through recombinant serotonin transporters; extracellular application of a PIP2-scavenging peptide mimicked this effect. PLC activation also diminished amphetamine-induced reverse transport without altering transmitter uptake. Inhibition of reverse transport by PLC activation was also observed in brain slices and with recombinant dopamine and noradrenaline, but not GABA transporters; rises in intracellular Ca2+ or activation of protein kinase C were not involved in these effects.


These data demonstrate for the first time PIP2 dependence of reverse transport and current in monoamine transporters.


Supported by FWF (P22893-B11, P17611, SFB3502, SFB3506), and a grant from NIH DA13975.