Cannabinoid receptors and their endogenous ligands.
Delta9-Tetrahydrocannabinol, a major psychoactive component of marijuana, has been shown to interact with specific cannabinoid receptors, thereby eliciting a variety of pharmacological responses in experimental animals and human. In 1990, the gene encoding a cannabinoid receptor (CB1) was cloned. This prompted the search for endogenous ligands. In 1992, N-arachidonoylethanolamine (anandamide) was isolated from pig brain as an endogenous ligand, and in 1995, 2-arachidonoylglycerol was isolated from rat brain and canine gut as another endogenous ligand. Both anandamide and 2-arachidonoylglycerol exhibit various cannabimimetic activities. The results of structure-activity relationship experiments, however, revealed that 2-arachidonoylglycerol, but not anandamide, is the intrinsic natural ligand for the cannabinoid receptor. 2-Arachidonoylglycerol is a degradation product of inositol phospholipids that links the function of cannabinoid receptors with the enhanced inositol phospholipid turnover in stimulated tissues and cells. The possible physiological roles of cannabinoid receptors and 2-arachidonoylglycerol in various mammalian tissues such as those of the nervous system are discussed.
Sugiura
Takayuki
T
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. sugiurat@pharm.teikyo-u.ac.jp
Waku
Keizo
K
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001665:Binding Sites; D063388:Endocannabinoids; D005989:Glycerides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000502:physiology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D008024:Ligands; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate; C078814:anandamide