Volume 8 Supplement 1

14th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Functional characterization of the novel cannabinoid receptor GPR55 and its modulation by CB1 and CB2 receptors

  • Nariman Balenga1,
  • Julia Kargl1,
  • Christopher M Henstridge2,
  • Andrew J Irving2 and
  • Maria Waldhoer1Email author
BMC Pharmacology20088(Suppl 1):A23

https://doi.org/10.1186/1471-2210-8-S1-A23

Published: 5 November 2008

We have recently shown that the G protein-coupled receptor 55 (GPR55) mediates intracellular effects of cannabinoids and other, non-cannabionid, ligands in addition to the classical cannabinoid 1 (CB1R) and 2 (CB2R) receptors. Here we show that the presence of either CB1R or CB2R alters the signaling pathways of GPR55. HEK-293 cells stably expressing either the GPR55 receptor alone or in combination with either CB1 (CB1/GPR55) or CB2 (CB2/GPR55) receptors were characterized in terms of signaling and receptor trafficking properties. To this end, FLEX calcium release, reporter gene and antibody feeding assays have been performed. Here we show that GPR55 is activated by lysophosphatidylinositol (LPI) and couples to Gα13, which in turn activates RhoA and RhoA kinase (ROCK). Moreover, we discovered that GPR55 activation leads to an efficient activation and nuclear translocation of nuclear factor of activated T-cells (NFAT) transcription factor family. We next tested a panel of known cannabinoid ligands and discovered that GPR55 is activated by AM251, which is a known inverse agonist on the CB1R. In addition, the CB1R antagonist SR141716A (rimonabant) was able to induce GPR55-mediated signaling, although it was less potent than both AM251 and LPI. LPI was also able to induce the internalization of GPR55. Lastly, we found that CB1R and CB2R co-localize with GPR55 on the surface of HEK cells and also can block the NFAT activation mediated by GPR55.

Authors’ Affiliations

(1)
Institute of Experimental and Clinical Pharmacology, Medical University of Graz
(2)
Centre for Neuroscience, Ninewells Hospital and Medical School, University of Dundee

Copyright

© Balenga et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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