GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current.
The CB(1) cannabinoid receptor mediates many of the psychoactive effects of Delta(9)THC, the principal active component of cannabis. However, ample evidence suggests that additional non-CB(1)/CB(2) receptors may contribute to the behavioral, vascular, and immunological actions of Delta(9)THC and endogenous cannabinoids. Here, we provide further evidence that GPR55, a G protein-coupled receptor, is a cannabinoid receptor. GPR55 is highly expressed in large dorsal root ganglion neurons and, upon activation by various cannabinoids (Delta(9)THC, the anandamide analog methanandamide, and JWH015) increases intracellular calcium in these neurons. Examination of its signaling pathway in HEK293 cells transiently expressing GPR55 found the calcium increase to involve G(q), G(12), RhoA, actin, phospholipase C, and calcium release from IP(3)R-gated stores. GPR55 activation also inhibits M current. These results establish GPR55 as a cannabinoid receptor with signaling distinct from CB(1) and CB(2).
Lauckner
Jane E
JE
Departments of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Jensen
Jill B
JB
Chen
Huei-Ying
HY
Lu
Hui-Chen
HC
Hille
Bertil
B
Mackie
Ken
K
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D063387:Cannabinoid Receptor Antagonists; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D004594:Electrophysiology; D004789:Enzyme Activation; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018408:Patch-Clamp Techniques; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D063387:Cannabinoid Receptor Antagonists; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054801:Phosphoinositide Phospholipase C; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein; D000077285:Rimonabant; D011188:Potassium; D002118:Calcium