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Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2428-33. Epub 2006 Feb 7.

N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties.

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  • 1Department of Medicinal Chemistry and Natural Products, Medical Faculty, and Laboratory of Environmental Physiology, Faculty of Dental Medicine, Hebrew University, Jerusalem 91120, Israel.

Abstract

The endocannabinoid N-arachidonoyl ethanolamine (anandamide), found both in the CNS and in the periphery, plays a role in numerous physiological systems. One might expect that the chemically related N-arachidonoyl-L-serine (ARA-S) could also be formed alongside anandamide. We have now isolated ARA-S from bovine brain and elucidated its structure by comparison with synthetic ARA-S. Contrary to anandamide, ARA-S binds very weakly to cannabinoid CB1 and CB2 or vanilloid TRPV1 (transient receptor potential vanilloid 1) receptors. However, it produces endothelium-dependent vasodilation of rat isolated mesenteric arteries and abdominal aorta and stimulates phosphorylation of p44/42 mitogen-activated protein (MAP) kinase and protein kinase B/Akt in cultured endothelial cells. ARA-S also suppresses LPS-induced formation of TNF-alpha in a murine macrophage cell line and in wild-type mice, as well as in mice deficient in CB1 or CB2 receptors. Many of these effects parallel those reported for abnormal cannabidiol (Abn-CBD), a synthetic agonist of a putative novel cannabinoid-type receptor. Hence, ARA-S may represent an endogenous agonist for this receptor.

PMID:
16467152
[PubMed - indexed for MEDLINE]
PMCID:
PMC1413724
Free PMC Article
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