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GPR55: signaling pathways and functions


We have recently shown that the G protein-coupled receptor 55 (GPR55) mediates intracellular effects of cannabinoids and other, non-cannabinoid ligands in addition to the classical cannabinoid 1 (CB1) and 2 (CB2) receptors. Here we show different signaling pathways triggered by GPR55 in response to a panel of its agonists. In addition the cytoskeleton rearrangement mediated by GPR55 is investigated.


HEK-293 cells stably expressing the GPR55 receptor were characterized in terms of signaling properties. To this end, FLEX calcium release, reporter gene, dynamic mass redistribution (DMR) and phalloidin actin staining assays have been performed.


Here we show that GPR55 is activated by lysophosphatidylinositol (LPI), AM251, SR141716A (rimonabant) and AM281. GPR55 activation induces intracellular calcium release, NF-κB, NFAT and CREB activation. Stimulation of GPR55 induces F-actin formation under the control of Gα13, RhoA and ROCK. We also show the suitability of Corning® Epic® DMR assay for GPR55 ligand screening.


GPR55 as the novel cannabinoid receptor triggers distinct signaling pathways in response to LPI and some classical CB1 receptor antagonists. Stress fiber formation mediated by GPR55 might show the function of this receptor in vivo.

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Correspondence to Maria Waldhoer.

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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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Balenga, N., Schröder, R., Kargl, J. et al. GPR55: signaling pathways and functions. BMC Pharmacol 9 (Suppl 2), A3 (2009).

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