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Manuel Guzmán Glioma 2009 THC autophagy double membrane

KW - Anandamide

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anandamide (AEA) and 2-arachidonoylglycerol ..

N2 - Endocannabinoids are regarded as retrograde signaling molecules at various types of synapses throughout the CNS. The lipid derivatives anandamide and 2-arachidonoylglycerol (2-AG) are generally thought to be the key molecular players in this process. Previous anatomical and electrophysiological studies provided compelling evidence that the biosynthetic enzyme of 2-AG is indeed localized in the postsynaptic plasma membrane, whereas its target, the CB 1 cannabinoid receptor, and the enzyme responsible for its inactivation are both found presynaptically. This molecular architecture of 2-AG signaling is a conserved feature of most synapses and supports the retrograde signaling role of 2-AG. Conversely, the molecular and neuroanatomical organization of synaptic anandamide signaling remains largely unknown. In contrast to its predicted role in retrograde signaling, here we show that N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD), a biosynthetic enzyme of anandamide and its related bioactive congeners, the N-acylethanolamines (NAEs), is concentrated presynaptically in several types of hippocampal excitatory axon terminals. Furthermore, high-resolution quantitative immunogold labeling demonstrates that this calcium-sensitive enzyme is localized predominantly on the intracellular membrane cisternae of axonal calcium stores. Finally, the highest density of NAPE-PLD is found in mossy terminals of granule cells, which do not express CB1 receptors. Together, these findings suggest that anandamide and related NAEs are also present at glutamatergic synapses, but the sites of their synthesis and action are remarkably different from 2-AG, indicating distinct physiological roles for given endocannabinoids in the regulation of synaptic neurotransmission and plasticity.

Fowler CJ: Anandamide uptake explained?Trends Pharmacol Sci. 33:181–185. 2012.  :  :

Starowicz K and Di Marzo V:Non-psychotropic analgesic drugs from the endocannabinoid system:'magic bullet' or 'multiple-target' strategies? Eur J Pharmacol.716:41–53. 2013. : :

2-Arachidonoylglycerol (2-AG) Induces Corneal …

demonstrated the enzymatic conversion of arachidonic acid toprostaglandin E2 ().Morrison WR et al.

Everley PA, Gartner CA, Haas W, Saghatelian A, Elias JE, Cravatt BF, Zetter BR, Gygi SP. (2007)Assessing enzyme activities using stable isotope labeling and mass spectrometry.
Mol Cell Proteomics. 6(10):1771-1777.

Wan Y, Saghatelian A, Chong LW, Zhang CL, Cravatt BF, Evans RM. (2007)Maternal PPAR-gamma protects nursing neonates by suppressing the production of inflammatory milk.
Genes Dev. 21(15):1895-1908.

The serine hydrolases MAGL, ABHD6 and ABHD12 as …

reported the identification of hydroxyalkanoates biologicalpolyesters containing carbon chains different from hydroxybutyrate ()

Studies on the amino acids in the vitamin K-dependent region of prothrombinindicate that vitamin K is involved in the derivatization of glutamic acid by

In a 2006 study, various human breast cancer cells (including the most aggressive known cell line,MDA-MB231) were treated in vitro with five natural phytocannabinoid compounds – cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid. Cannabidiol was shown to be the most effective inhibitor of neoplastic cell proliferation, and was effective even at very low molecular concentration.

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  • {Cellular/Molecular The Endocannabinoid 2-Arachidonoylglycerol ..

    Saghatelian A, Cravatt BF. (2005) Assignment of protein function in the postgenomic era.Nat Chem Biol. 1(3):130-142.

  • evidence for on-demand biosynthesis of 2-arachidonoylglycerol

    Anandamide - Wikipedia

  • The Cravatt Lab - The Scripps Research Institute

    2-Arachidonoylglycerol ( 2-AG ) is an endocannabinoid , an endogenous agonist of the CB receptor

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Endocannabinoids: Control of Food Intake & Energy Balance

Chamero P, Marton TF, Logan DW, Flanagan K, Cruz JR, Saghatelian A, Cravatt BF, Stowers L. (2007)Identification of protein pheromones that promote aggressive behaviour.
Nature. 450(7171):899-902.

Arachidonic acid: contents in brief - Tuscany Diet

Carlson EE, Cravatt BF. (2007)Enrichment tags for enhanced-resolution profiling of the polar metabolome.
J Am Chem Soc. Dec 5. 129(51):15780-2.


Blankman JL, Simon GM, Cravatt BF. (2007)A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol.
Chem Biol. 14(12):1347-1356.

Cannabis Oil & Cancer; The Theory

Wise LE, Cannavacciulo R, Cravatt BF, Martin BF, Lichtman AH. (2008)valuation of fatty acid amides in the carrageenan-induced paw edema model.
Neuropharmacology. 54(1):181-8.

Eosinophilic Inflammation in Asthma — NEJM

Batkai S, Rajesh M, Mukhopadhyay P, Hasko G, Liaudet L, Cravatt BF, Csiszar A, Ungvari ZI, PacherP. (2007) Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory geneexpressionand apoptosis in mice lacking fatty acid amide hydrolase.
Am J Physiol Heart Circ Physiol. 293(2):H909-H918.

Lipids in Action - Their Biological Functions - …

demonstrated that nearly allphosphatidylserine and a minimum of 70% of phosphatidylethanolamine is on theinside surface of the human erythrocyte membrane, thus "presenting a strongevidence for an asymmetric arrangement of phospholipids" ().

First demonstration of an inhibition of sterol biosynthesis (HMG-CoA reductaseactivity) by oxygenated derivatives of cholesterol in cultured mammalian cells ().

For the first time, the existence of polyunsaturated fatty acids was reported inmarine bacteria ().

Important dates in the history of lipids ..

Maccarrone M, Rossi S, Bari M, De Chiara V, Fezza F, Musella A, Gasperi V, Prosperetti C, Bernardi G,Finazzi-Agro A, Cravatt BF, Centonze D. (2008)Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum.
Nat Neurosci. 11(2):152-159.

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