THE BINDING OF NOVEL PHENOLIC DERIVATIVES OF ANANDAMIDE TO BRAIN CANNABINOID RECEPTORS

Citation
Ws. Edgemond et al., THE BINDING OF NOVEL PHENOLIC DERIVATIVES OF ANANDAMIDE TO BRAIN CANNABINOID RECEPTORS, Prostaglandins, leukotrienes and essential fatty acids, 52(2-3), 1995, pp. 83-86
Citations number
15
Categorie Soggetti
Endocrynology & Metabolism",Biology
ISSN journal
09523278
Volume
52
Issue
2-3
Year of publication
1995
Pages
83 - 86
Database
ISI
SICI code
0952-3278(1995)52:2-3<83:TBONPD>2.0.ZU;2-F
Abstract
Arachidonylethanolamide (N-2-hydroxyethyl-arachidonamide) or 'anandami de' is a naturally occurring derivative of arachidonic acid that has b een shown to bind and activate cannabinoid receptors in the brain, Sin ce other potent ligands for the cannabinoid receptor have an aromatic hydroxyl group, we investigated the hypothesis that replacement of the ethanolamine hydroxyl with an aromatic hydroxyl will increase the bin ding affinity for the cannabinoid receptor. Two novel congeners of ana ndamide containing aromatic hydroxyl groups were synthesized: N-2-(4-h ydroxyphenyl)ethyl arachidonamide (HEA) and N-2-hydroxyphenyl arachido namide (HPA). The affinity of these congeners for the brain cannabinoi d receptor was determined by competition with [H-3]CP55940. HEA compet ed for [H-3]CP55940 binding with a K-i of 600 nM; HPA had a K-i of 220 0 nM. These results indicate that increased size in the amide portion of anandamide decreases affinity for the receptor, Phenylmethylsulfony l flouride (PMSF), an inhibitor of anandamide catabolism by brain memb ranes, had no effect on the binding of either HEA or HPA, We conclude that these congeners are not substrates for the amidase that cataboliz es anandamide.