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


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.

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Correspondence to Harald H Sitte.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is 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.

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Buchmayer, F., Schicker, K., Stübiger, G. et al. Amphetamine actions rely on the availability of phosphatidylinositol-4,5-bisphosphate. BMC Pharmacol 11 (Suppl 2), A19 (2011).

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