Endocannabinoids and extracts of the cannabis plant C. sativa affect a plethora of biological processes via CB1 and CB2 receptors. However, much evidence has emerged to suggest that additional receptors exist that mediate certain cannabinoid functions. Here we show that mammalian and plant derived cannabinoid ligands bind to and affect the activity of the orphan G-protein coupled receptor (GPCR) GPR55. In turn this results in activation of the intracellular signaling mediators RhoA, Rac1 and cdc42 via activation of G13 G-proteins. RT-PCR expression analysis, immunohistochemistry and in situ hybridisation have been used to reveal the tissue distribution of GPR55. In vivo, a GPR55 selective agonist, O1602, induces a reduction in blood pressure in spontaneously hypertensive rats. This effect is significantly enhanced by concomitant selective CB1 receptor blockade, and is sensitive to a GPR55 selective antagonist. These data suggest that GPR55 is a novel cannabinoid receptor that may play a role in blood pressure regulation.
Life Sciences 2007 (2007) Proc Life Sciences, SA230
Research Symposium: A new receptor for cannabinoid ligands
P. Greasley1, E. Ryberg1, A. Lindblom1, A. Åstrand1, N. Larsson1, S. Hjorth1, S. Sjögren1
1. AstraZeneca, Mölndal, Sweden.
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