Anandamide

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Anandamide
Chemical name	(5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl) icosa-5,8,11,14-tetraenamide or arachidonoylethanolamide
Chemical formula	C₂₂H₃₇NO₂
Molecular mass	347.53 g/mol
CAS number	94421-68-8
SMILES	CCCCC\C=C/C\C=C/C\C=C /C\C=C/CCCC(NCCO)=O
Image:Anandamide.svg

Anandamide, also known as arachidonoylethanolamide or AEA, is an endogenous cannabinoid neurotransmitter found in animal and human organs, especially in the brain. It was isolated and its structure was elucidated by Czech analytical chemist Lumír Ondřej Hanuš and American molecular pharmacologist William Anthony Devane in the Laboratory of Raphael Mechoulam, at the Hebrew University in Jerusalem in 1992. The name is taken from the Sanskrit word ananda, which means "bliss, delight", and amide. <ref>Devane W. A., Hanuš L., Breuer A., Pertwee R. G., Stevenson L. A., Griffin G., Gibson D., Mandelbaum A., Etinger A., Mechoulam R.: Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946-1949 (1992)</ref> <ref>Mechoulam R., Fride E.: The unpaved road to the endogenous brain cannabinoid ligands, the anandamides in “Cannabinoid Receptors” (ed. R. Pertwee), Academic Press, London. Pp. 233-258 (1995)</ref>

1 Cannabinoid receptors
2 Endogenous and dietary sources
3 See also
4 References
5 External links

[edit] Cannabinoid receptors

Anandamide's effects can be either central, in the brain, or peripheral, in other parts of the body. These distinct effects are mediated primarily by CB1 cannabinoid receptors in the nervous system, and CB2 cannabinoid receptors in the periphery. The latter is mainly involved in functions of the immune system.

Cannabinoid receptors are part of the largest known family of receptors, the G protein-coupled receptors, which - in this case - has a distinctive pattern in which the receptor molecule spans the cell membrane seven times over. The CB1 receptor is one of the most numerous G protein-coupled receptors in the nervous system.

Cannabinoid receptors were originally discovered as being sensitive to Δ⁹-tetrahydrocannabinol (Δ⁹-THC), which is the primary psychoactive cannabinoid found in cannabis. The discovery of anandamide came from research into CB1 and CB2, as it was inevitable that a naturally occurring (endogenous) chemical would be found to affect these receptors.

Anandamide has been shown to be involved in working memory<ref>Mallet PE, Beninger RJ. The endogenous cannabinoid receptor agonist anandamide impairs memory in rats. Behav Pharmacol. 1996; 7:276-284.</ref>. Studies are under way to explore what role anandamide plays in human behavior, such as eating and sleep patterns, and the part it plays in pain relief.

Anandamide is also important for implantation of the early stage embryo in its blastocyst form into the uterus. Therefore cannabinoids such as Δ⁹-THC might interfere with the earliest stages of human pregnancy<ref>Piomelli D. THC: moderation during implantation. Nat Med. 2004 Jan;10(1):19-20. PMID 14702623</ref>.

Moreover, anandamide is thought to be an endogenous ligand for vanilloid receptors (which are involved in the transduction of acute and inflammatory pain signals), activating the receptor in a PKC-dependent (protein kinase C-dependent) manner.

Image:LumRaf.jpg

[edit] Endogenous and dietary sources

Endogenous cannabinoids occur in minute quantities in cocoa (fermented Theobroma cacao) beans, in sea urchin roe<ref>Bisogno T, Ventriglia M, Milone A, Mosca M, Cimino G, Di Marzo V. Occurrence and metabolism of anandamide and related acyl-ethanolamides in ovaries of the sea urchin Paracentrotus lividus. Biochim Biophys Acta. 1997 Apr 21;1345(3):338-48. PMID 9150253</ref>, and in chocolate, though there is some controversy over whether they have any effects on the body in these quantities.

The human body synthesizes anandamide from N-arachidonoyl phosphatidylethanolamine, which is itself made by transferring arachidonic acid from phosphatidylcholine (PC) to the free amine of phosphatidylethanolamine (PE).<ref>V Natarajan, PV Reddy, PC Schmid, HH Schmid, N-Acylation of ethanolamine phospholipids in canine myocardium, Biochem. Biophys. Acta, 1982, Vol 712, 342-355, PMID 7126608</ref><ref>H Cadas, E di Tamaso, D Piomelli, Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain., J Neurosci, 1997, Vol 17(4), 1226-42. PMID 9006968</ref> Endogenous anandamide is present at very low levels and has a very short half-life due to the action of the enzyme fatty acid amide hydrolase which breaks it down into free arachidonic acid and ethanolamine. Studies of piglets show that dietary levels of AA and other essential fatty acids affect the levels of anandamide and other endocannabinoids in the brain. <ref>Alvin Berger, Anandamide and diet: Inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets, PNAS, May 22, 2001 vol. 9, no. 11, http://www.pnas.org/cgi/content/abstract/98/11/6402</ref>