Signal transduction of eicosanoid CB1 receptor ligands

The eicosanoid ligand, arachidonylethanolamide (anandamide), interacts with the CB1 cannabinoid receptor in the brain to signal its response. Pharmaco phoric points of interaction between this agonist and the receptor have bee n proposed based upon structure-activity relationship studies of ligand bin ding to the receptor. Three dimensional quantitative structure-activity rel ationship (3D-QSAR) models have been constructed based upon the correspondi ng pharmacophoric points predicted for cannabinoid ligands Delta(9)-tetrahy drocannabinol and 9-nor-9 beta-hydroxyhexa-hydrocannabinol. A novel data se t has been used to test the statistical validity of these models. Once the ligand interacts with the CB1 receptor, signal tranduction occurs via G-pro teins of the Gi/o family which are shown to be associated with the receptor . Evidence suggests that the juxtamembrane region of the C-terminal of the CB1 receptor is critical for activation of these G-proteins.