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

Mechoulam, Raphael; Ben‐Shabat, Shimon; Hanŭs, L; Ligumsky, M.; Kaminski, Norbert E.; Schatz, Anthony R.; Gopher, Asher; Almog, Shlomo; Martin, Billy R.; Compton, David R.; Pertwee, Roger G.; Griffin, Graeme; Bayewitch, Michael; Barg, Jacob; Vogel, Zvi

doi:10.1016/0006-2952(95)00109-d

Cited by 2,540 publications

(1,575 citation statements)

References 22 publications

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“…2-AG and anandamide are two of the putative endocannabinoids presumed to mediate the effects of CB1Rs in the CNS (Devane et al, 1992;Mechoulam et al, 1995;Sugiura et al, 1995; for a review Di Marzo et al, 1998;Piomelli et al, 2000).…”

Section: The G-protein Coupled Receptor Pathway Of Retrograde Inhibitionmentioning

confidence: 99%

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

Diana

Marty

2004

British J Pharmacology

230

167

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Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE) are two related forms of short-term synaptic plasticity of GABAergic and glutamatergic transmission, respectively. They are induced by calcium concentration increases in postsynaptic cells and are mediated by the release of a retrograde messenger, which reversibly inhibits afferent synapses via presynaptic mechanisms. We review here:(1) The evidence accumulated during the 1990s that has led to the conclusion that DSI/DSE rely on retrograde signaling. (2) The more recent research that has led to the identification of endocannabinoids as the retrograde messengers responsible for DSI/DSE. (3) The possible mechanisms by which presynaptic type 1 cannabinoid receptors reduce synaptic efficacy during DSI/DSE. (4) The possible modes of induction of DSI/DSE by physiological activity patterns, and the partially conflicting evaluations of the calcium concentration increases required for cannabinoid synthesis. (5) Finally, the relation between DSI/DSE and other forms of long-and short-term synaptic inhibition, which were more recently associated with the production of endocannabinoids by postsynaptic cells.We conclude that recent studies on DSI/DSE have uncovered a specific and original mode of action for endocannabinoids in the brain, and that they have opened new avenues to understand the role of retrograde signaling in central synapses.

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Section: The G-protein Coupled Receptor Pathway Of Retrograde Inhibitionmentioning

confidence: 99%

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

Diana

Marty

2004

British J Pharmacology

230

167

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“…Endocannabinoids are bioactive lipids released from the cell membrane upon cell activation. The two main endocannabinoids are the arachidonic acid (AA) derivatives 2‐arachidonoylglycerol (2‐AG) 13 and N ‐arachidonoylethanolamine (anandamide (AEA)) 14. Most of their actions are mediated by two G‐protein‐coupled receptors, the cannabinoid receptors 1 and 2 (CB 1 and CB 2 ).…”

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confidence: 99%

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Frei

Luschnig

Parzmair

et al. 2016

Allergy

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BackgroundAccumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2‐arachidonoylglycerol (2‐AG) has been proposed to elicit eosinophil migration in a CB 2 receptor/Gi/o‐dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2‐AG into eicosanoids. Here, we explored the direct contribution of specific CB 2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo.Methods In vitro studies including CB 2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow‐derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA‐induced asthma and directed eosinophil migration.Results CB 2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB 2 receptor agonist JWH‐133 induced a moderate migratory response in eosinophils. However, short‐term exposure to JWH‐133 potently enhanced chemoattractant‐induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB 2 knockout mice and by using the selective CB 2 antagonist SR144528. Of note, systemic application of JWH‐133 clearly primed eosinophil‐directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB 2‐specific manner. This effect was completely absent in eosinophil‐deficient ∆dblGATA mice.ConclusionOur data indicate that CB 2 may directly contribute to the pathogenesis of eosinophil‐driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB 2‐mediated priming of eosinophils. Hence, antagonism of CB 2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.

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“…Metabolism of anandamide happens rapidly by fatty acid amide hydrolase (FAAH) 31, 43. 2‐AG was discovered shortly after anandamide in 1995 44, 45. It is synthesized by the enzyme diacylglycerol lipase from arachidonic acid‐containing diacylglycerol and metabolized by soluble monoacylglycerol lipase 31, 46.…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Cannabinoids, the Heart of the Matter

Alfulaij

Meiners

Michalek

et al. 2018

JAHA

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

Cited by 2,540 publications

References 22 publications

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Cannabinoids, the Heart of the Matter

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