The orphan receptor GPR55 is a novel cannabinoid receptor.
Ryberg, E 1; Larsson, N 1; Sjogren, S 2; Hjorth, S 3; Hermansson, N-O 1; Leonova, J 1; Elebring, T 4; Nilsson, K 4; Drmota, T 1; Greasley, P J 1*
[Article]
British Journal of Pharmacology.
152(7):1092-1101, December 2007.
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Background: The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes.
Experimental approach: Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTP[gamma]S binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the G-protein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways.
Key results: We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTP[gamma]S binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to G[alpha]13 and can mediate activation of rhoA, cdc42 and rac1.
Conclusions: These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s).
Copyright (C) 2007 John Wiley & Sons, Inc.
