J Vet Sci.  2002 Sep;3(3):179-184.

SR144528 as Inverse Agonist of CB2 Cannabinoid Receptor

• Rhee MH
• Kim SK

Abstract

It is now well established that several G protein- coupled receptors can signal without agonist stimulation (constitutive receptors). Inverse agonists have been shown to inhibit the activity of such constitutive G protein-coupled receptor signaling. Agonist activation of the Gi/o-coupled peripheral cannabinoid receptor CB2 normally inhibits adenylyl cyclase type V and stimulates adenylyl cyclase type II. Using transfected COS cells, we show here that application of SR144528, an inverse agonist of CB2, leads to a reverse action (stimulation of adenylyl cyclase V and inhibition of adenylyl cyclase II). This inverse agonism of SR144528 is dependent on the temperature, as well as on the concentration of the cDNA of CB2 transfected. Pertussis toxin blocked the regulation of adenylyl cyclase activity by SR 144528.

Keyword

Cannabinoids; CB2 cannabinoid receptor; SR144528; Inverse agonism; G protein Adenylyl cyclase

MeSH Terms

Adenylate Cyclase/antagonists&inhibitors/genetics/metabolism
Animals
Binding, Competitive
Bornanes/metabolism/*pharmacology
COS Cells
Cannabinoids/metabolism
Cercopithecus aethiops
Isoenzymes/antagonists&inhibitors/genetics/metabolism
Pyrazoles/metabolism/*pharmacology
Rats
*Receptor, Cannabinoid, CB2
Receptors, Cannabinoid
Receptors, Drug/agonists/*antagonists&inhibitors/genetics/metabolism
Signal Transduction/drug effects/physiology
Transfection