The orphan receptor GPR55 is a novel cannabinoid receptor

Area of Science:

• Pharmacology
• Molecular Biology
• Neuroscience

Background:

• The endocannabinoid system, involving CB1 and CB2 receptors, regulates physiological processes.
• Emerging evidence suggests additional receptors are involved in cannabinoid ligand activity.

Purpose of the Study:

• To investigate the role of GPR55 as a potential novel cannabinoid receptor.
• To characterize the binding and signaling properties of GPR55.

Main Methods:

• Transfected cells expressing human GPR55 were used to assess binding of cannabinoid ligands.
• Guanosine triphosphate gamma-sulfide (GTPγS) binding assays were performed.
• Antibody and peptide blocking determined G-protein coupling, with downstream signaling pathways measured.

Main Results:

• GPR55 was shown to bind and be activated by the cannabinoid ligand CP55940.
• Endocannabinoids like anandamide and virodhamine activated GTPγS binding via GPR55 with nanomolar potency.
• Cannabidiol and abnormal cannabidiol, lacking CB1/CB2 activity, also activated GPR55.
• GPR55 couples to Galpha13, mediating activation of rhoA, cdc42, and rac1.

Conclusions:

• GPR55 functions as a novel cannabinoid receptor.
• The identified ligand profile of GPR55 provides a basis for understanding its physiological roles.