Noladin ether, a putative novel endocannabinoid: inactivation mechanisms and a sensitive method for its quantification in rat tissues

  title={Noladin ether, a putative novel endocannabinoid: inactivation mechanisms and a sensitive method for its quantification in rat tissues},
  author={Filomena Fezza and Tiziana Bisogno and Alberto Minassi and Giovanni Appendino and Raphael Mechoulam and Vincenzo Di Marzo},
  journal={FEBS Letters},

Ether‐linked analogue of 2‐arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species

It is found that 2‐AG ether is not present, at least in an appreciable amount, in the rat brain by gas chromatography‐mass spectrometry analysis and fluorometric high performance liquid chromatography analysis.

Resorcinol-sn-glycerol derivatives: novel 2-arachidonoylglycerol mimetics endowed with high affinity and selectivity for cannabinoid type 1 receptor.

The cannabinoid receptor binding properties, the CB1 functional activity, and the stability to plasma esterases of a novel series of compounds characterized by the conversion of the amide head into the glycerol-ester or glycerl-ether head, typical of 2-AG or the "putative" endocannabinoid 2-AGE, respectively are explored.

The endocannabinoid system: a general view and latest additions

The latest ‘additions’ to the endocannabinoid system are reviewed together with earlier breakthroughs that have contributed to the present knowledge of the biochemistry and pharmacology of theendocannabinoids.

Simultaneous determination of 2-arachidonoylglycerol, 1-arachidonoylglycerol and arachidonic acid in mouse brain tissue using liquid chromatography/tandem mass spectrometry.

A sensitive and specific quantification method is developed for simultaneous determination of 2-AG, 1-AG and AA from mouse brain and adipose tissues by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using a simple brain sample preparation method.

A simple LC-MS/MS method for the simultaneous quantification of endocannabinoids in biological samples.

Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid.

Noladin ether degraded more slowly than either 2-AG or AEA in the iris-ciliary body and cornea homogenates, probably because of its more stable chemical structure.

Determination of endocannabinoids in nematodes and human brain tissue by liquid chromatography electrospray ionization tandem mass spectrometry.

The Endocannabinoid Noladin Ether Acts as a Full Agonist at Human CB2 Cannabinoid Receptors

Surprisingly, in transfected CHO cells, NE exhibits a relatively high nanomolar affinity for CB2 receptors, comparable to that observed for the endocannabinoid 2-arachidonoyl glycerol (2-AG) (Ki = 1016 nM), which indicates that NE acts as a full agonist at human CB2 receptor and thus might have important physiological functions at peripheral cannabinoid receptors.



The novel endogenous cannabinoid 2-arachidonoylglycerol is inactivated by neuronal- and basophil-like cells: connections with anandamide.

The hydrolysis of 2-AG was inhibited by typical esterase inhibitors and by more specific blockers of 'fatty acid amide hydrolase' (FAAH), the enzyme catalysing the hydrolyses of the other 'endocannabinoid', anandamide (AEA).

Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function.

The hypothesis that, in the brain, AEA is a metabolic product of NArPE and may reach levels compatible with its proposed neuromodulatory function is supported.

Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells.

The results suggest that the Ca2+-induced formation of 2-AG proceeds through the intermediacy of AcAGs but not necessarily through phospholipase C activation, and supports the hypothesis that this cannabimimetic monoacylglycerol might be a physiological neuromodulator.

2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor

Two types of endogenous cannabinoid-receptor agonists have been identified thus far and an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain is reported.

Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.

Biosynthesis of anandamide and related acylethanolamides in mouse J774 macrophages and N18 neuroblastoma cells.

It is suggested for the first time that AnNH is biosynthesized via the same mechanism in a non-neuronal cell line, mouse J774 macrophages, together with other acylethanolamides and is possibly involved in the control of the immune/inflammatory response.

Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides

It is shown that oleamide hydrolase may serve as the general inactivating enzyme for a growing family of bioactive signalling molecules, the fatty-acid amides6–8, and the structure and sleep-inducing properties of cis-9-octadecenamide, a lipid isolated from the cerebrospinal fluid of sleep-deprived cats are reported.

The uptake by cells of 2-arachidonoylglycerol, an endogenous agonist of cannabinoid receptors.

Study of the facilitated transport of [14C]AEA and [3H]2-AG into rat C6 glioma cells found uptake mechanisms with different efficacies but similar affinities for the two compounds, suggesting that transport into C6 cells limits the action of both endocannabinoids.

2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.

2-Arachidonoylglycerol was shown to bind appreciably to the cannabinoid receptor in competitive inhibition experiments and may be an endogenous cannabinoid receptor ligand in the brain.