SR144528 as Inverse Agonist of CB2 Cannabinoid Receptor.
- Author:
Man Hee RHEE
1
;
Sang Keun KIM
Author Information
1. Department of Cell Biology & Physiology, Washington University School of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Cannabinoids;
CB2 cannabinoid receptor;
SR144528;
Inverse agonism;
G protein Adenylyl cyclase
- MeSH:
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
- From:Journal of Veterinary Science
2002;3(3):179-184
- CountryRepublic of Korea
- Language:English
-
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.
