Measurement of inverse agonism of the cannabinoid receptors.
The cannabinoid receptors are G protein-coupled receptors that are activated by endocannabinoids or exogenous agonists such as tetrahydrocannabinol. Upon agonist binding, cannabinoid receptors will activate Gi which in turn inhibits adenylyl cyclase. Recently, inverse agonists for the cannabinoid receptors have been identified, demonstrating constitutive activity of the cannabinoid receptors. Several methods have been used to measure inverse agonist activity of ligands for the cannabinoid receptors, including Gi-cAMP second messenger assay, GTPγS binding assay, and electrophysiological assays. Each assay has its advantages and limitations, and the Gi-cAMP second messenger assay appears to provide the best overall measurement of inverse agonism in a cellular environment.
Department of Pharmacology, Forest Research Institute, Harborside Financial Center, Jersey City, New Jersey, USA.
Tung M
TM
Fong
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D054314:Drug Inverse Agonism; D004594:Electrophysiology / Q000379:methods; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D043882:Receptors, Cannabinoid / Q000378:metabolism*
D043882:Receptors, Cannabinoid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP