Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1863, Issue 11, Pages 1433-1440Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2018.08.003
Keywords
Anandamide; Endocannabinoids; Cannabinoid receptors; Vanilloid receptors; Fatty acid amide hydrolase; Polyunsaturated fatty acids
Funding
- Prince Sattam bin Abdulaziz University
- Kingdom of Saudi Arabia
- Biotechnology and Biological Sciences Research Council
- Philadelphia University, Jordan
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Anandamide, the first identified endogenous cannabinoid and TRPV1 agonist, is one of a series of endogenous N-acylethanolamines, NAEs. We have generated novel assays to quantify the levels of multiple NAEs in biological tissues and their rates of hydrolysis through fatty acid amide hydrolase. This range of NAEs was also tested in rapid response assays of CB1, CB2 cannabinoid and TRPV1 receptors. The data indicate that PEA, SEA and OEA are not endocannabinoids or endovanilloids, and that the higher endogenous levels of these metabolites compared to polyunsaturated analogues are a correlate of their slow rates of hydrolysis. The n - 6 NAEs (AEA, docosatetraenoyl and docosapentaenoyl derivatives) activated both CB(1 )and CB2 receptors, as well as TRPV1 channels, suggesting them to be 'genuine' endocannabinoids and `endovanilloids'. The n - 3 NAEs (eicosapentaenoyl, docosapentaenoyl and docosahexaenoyl derivatives) activated CB 2 receptors and some n - 3 NAEs (docosapentaenoyl and docosahexaenoyl derivatives) also activated TRPV1 channels, but failed to activate the CB I receptor. We hypothesise that the preferential activation of CB2 receptors by n - 3 PUFA NAEs contributes, at least in some part, to their broad anti-inflammatory profile.
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