Formation and inactivation of endogenous cannabinoid anandamide in central neurons

@article{Marzo1994FormationAI,
  title={Formation and inactivation of endogenous cannabinoid anandamide in central neurons},
  author={Vincenzo Di Marzo and Angelo Fontana and Hugues Cadas and Sergio Schinelli and Guido Cimino and J-C. Schwartz and D. Piomelli},
  journal={Nature},
  year={1994},
  volume={372},
  pages={686-691}
}
ANANDAMIDE (N-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors1–4, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through… Expand
Biosynthesis of an Endogenous Cannabinoid Precursor in Neurons and its Control by Calcium and cAMP
TLDR
The results thus indicate that NAPE levels in cortical neurons are controlled by Ca2+ ions and cAMP, and regulatory effect may participate in maintaining a supply of cannabimimetic N-acylethanolamines during synaptic activity, and prime target neurons for release of these bioactive lipids. Expand
Receptor-dependent formation of endogenous cannabinoids in cortical neurons.
TLDR
The findings indicate that cortical neurons produce anandamide and 2-arachidonylglycerol in a receptor-dependent manner, and that brain neurons may generate different endocannabinoid lipids depending on their complement of neurotransmitter receptors. Expand
Anandamide as an intracellular messenger regulating ion channel activity
Abstract The endocannabinoid anandamide ( N -arachidonoylethanolamine) was proposed to be an extracellular retrograde messenger, which regulates excitability of neurons by cannabinoid CB 1Expand
Anandamide as an intracellular messenger regulating ion channel activity.
TLDR
The intriguing possibility that anandamide, prior to its release into the synaptic cleft, may regulate ion homeostasis and excitability of neurons as an intracellular modulator of ion channels independent of its action at cannabinoid CB1 receptors is reviewed. Expand
Endogenous cannabinoid ligands--chemical and biological studies.
TLDR
A monoglyceride, 2-arachidonyl-glycerol which binds to both CB1 and CB2 in transfected cells and inhibits andenylate cyclase in spleen cells was found in the gut, and its role is apparently associated with the immune system. Expand
Brain and peripheral anandamide amidohydrolase and its inhibition by synthetic arachidonate analogues.
TLDR
The preliminary characterization of FAAH-like enzymatic activities from a blood cell type, the rat basophilic leukemia (RBL-1) cell line, and from other peripheral mammalian and invertebrate cells are reported, and the effect of five synthetic AA-derived inhibitors on these enzymes as well as on the previously described amidohydrolases are described. Expand
Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells.
TLDR
It is concluded that anandamide transport in the RBL-2H3 cells is carrier-mediated, and uptake in peripheral cells is functionally and pharmacologically identical with that observed in neurons and astrocytes. Expand
Anandamide produced by Ca2+-insensitive enzymes induces excitation in primary sensory neurons
TLDR
It is shown for the first time, that cultured rat primary sensory neurons express at least four of the five known Ca2+-insensitive enzymes implicated in the synthesis of anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl results in anandamia production which is not changed by the removal of extracellular Ca2+. Expand
Biochemistry and pharmacology of arachidonylethanolamide, a putative endogenous cannabinoid.
TLDR
The hypothesis that N-arachidonylethanolamine (AEA), also called anandamide, is synthesized in the brain and functions as an endogenous ligand of the cannabinoid receptor is presented and some evidence to support this hypothesis is explored. Expand
Biosynthesis of 2-arachidonoyl-glycerol, a novel cannabimimetic eicosanoid, in mouse neuroblastoma cells.
Following the original isolation from porcine brain of the first endogenous ligand of cannabinoid receptors, anandamide (arachidonoyl-ethanolamide)1, another arachidonic acid (AA)-derived metabolite,Expand
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