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. Pharmacophoric points of interaction between this agonist and the receptor have been proposed based upon structure-activity relationship studies of ligand binding to the receptor. Three dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed based upon the corresponding pharmacophoric points predicted for cannabinoid ligands delta9-tetrahydrocannabinol and 9-nor-9beta-hydroxyhexa-hydrocannabinol. A novel data set has been used to test the statistical validity of these models. Once the ligand interacts with the CB1 receptor, signal transduction occurs via G-proteins 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.
Howlett
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AC
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, MO 63104, USA. howletta@slu.edu
Mukhopadhyay
S
S
Shim
J Y
JY
Welsh
W J
WJ
D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism*; D002186:Cannabinoids; D063388:Endocannabinoids; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D015398:Signal Transduction
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D008024:Ligands; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D019204:GTP-Binding Proteins; C078814:anandamide