Elsevier

Neurobiology of Disease

Volume 5, Issue 6, December 1998, Pages 386-404
Neurobiology of Disease

Regular Article
Biochemistry of the Endogenous Ligands of Cannabinoid Receptors,☆☆

https://doi.org/10.1006/nbdi.1998.0214Get rights and content

Abstract

In 1992 the discovery of the first endogenous ligand of cannabinoid receptors, anandamide, provided conclusive support to the hypothesis that an “endogenous cannabinoid regulatory system” exists in mammalian nervous tissue. Anandamide (N-arachidonoyl-ethanolamine) was the first of a series of long-chain fatty acid derivatives, including two other polyunsaturatedN-acylethanolamines and 2-arachidonoyl-glycerol, found to exert cannabimimetic properties in either central or peripheral tissues. Here we review the current knowledge on the biochemical bases of the formation and inactivation of endogenous cannabinoid ligands as well as of their interaction with cannabinoid receptor subtypes.

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    Abbreviations used: 2-AG, 2-arachidonoyl-glycerol; CB1, cannabinoid receptor 1; CB2, cannabinoid receptor 2; SAR, structure–activity relationship;N-ArPE,N-arachidonoylphosphatidylethanolamine; DAG,sn-2-arachidonate containing diacylglycerols; FAAH, fatty acid amide hydrolase; PMSF, phenylmethylsulfonyl fluoride; NEM,N-ethylmaleimide; ATFMK, arachidonoyltrifluoromethyl ketone; MAFP, methylarachidonoyl fluorophosphonate; cannabimimetic, acting cannabinoid-like; endocannabinoids, compounds which occur endogenously (i.e., anandamide) and act cannabimimetically by binding to cannabinoid receptors.

    ☆☆

    D. E. VanceJ. Vance

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