ArticleThe Journal of physiology2013
Acute inhibition of diacylglycerol lipase blocks endocannabinoid-mediated retrograde signalling: evidence for on-demand biosynthesis of 2-arachidonoylglycerol.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 62 citations in OpenAlex.
- Impact of Elovl5 Deficiency on Cerebellar Excitatory Synaptic Transmission in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Correlation Between In Silico Docking/Simulation Results and In Vitro MAGL Inhibition Potency of Selected Triterpenes.Current issues in molecular biology · 2025Article
- Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.Molecular pharmacology · 2025Article
- Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.The Journal of pharmacology and experimental therapeutics · 2024Review
- Endocannabinoid-mediated rescue of somatosensory cortex activity, plasticity and related behaviors following an early in life concussion.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of diacylglycerol lipase β modulates lipid and endocannabinoid levels in theFrontiers in endocrinology · 2023Article
- Mechanisms of endocannabinoid transport in the brain.British journal of pharmacology · 2022Review
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- 2-Arachidonoylglycerol mobilization following brief synaptic stimulation in the dorsal lateral striatum requires glutamatergic and cholinergic neurotransmission.Neuropharmacology · 2022Article
- Fatty Acid-Binding Protein 5 Modulates Brain Endocannabinoid Tone and Retrograde Signaling in the Striatum.Frontiers in cellular neuroscience · 2022Article
- Axonal CB1 Receptors Mediate Inhibitory Bouton Formation via cAMP Increase and PKA.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Glial Cell AMPA Receptors in Nervous System Health, Injury and Disease.International journal of molecular sciences · 2019Review
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- Emerging Trends in Retrograde Signaling.Molecular neurobiology · 2016Review
- Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders.Nature communications · 2016Article
- Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Highly Selective, Reversible Inhibitor Identified by Comparative Chemoproteomics Modulates Diacylglycerol Lipase Activity in Neurons.Journal of the American Chemical Society · 2015Article
- Cerebellar endocannabinoids: retrograde signaling from purkinje cells.Cerebellum (London, England) · 2015Review
- Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.Nature reviews. Neuroscience · 2015Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) produced by diacylglycerol lipase α (DGLα) is one of the best-characterized retrograde messengers at central synapses. It has been thought that 2-AG is produced 'on demand' upon activation of postsynaptic neurons. However, recent studies propose that 2-AG is pre-synthesized by DGLα and stored in neurons, and that 2-AG is released from such 'pre-formed pools' without the participation of DGLα. To address whether the 2-AG source for retrograde signalling is the on-demand biosynthesis by DGLα or the mobilization from pre-formed pools, we examined the effects of acute pharmacological inhibition of DGL by a novel potent DGL inhibitor, OMDM-188, on retrograde eCB signalling triggered by Ca(2+) elevation, Gq/11 protein-coupled receptor activation or synergy of these two stimuli in postsynaptic neurons. We found that pretreatment for 1 h with OMDM-188 effectively blocked depolarization-induced suppression of inhibition (DSI), a purely Ca(2+)-dependent form of eCB signalling, in slices from the hippocampus, striatum and cerebellum. We also found that at parallel fibre-Purkinje cell synapses in the cerebellum OMDM-188 abolished synaptically induced retrograde eCB signalling, which is known to be caused by the synergy of postsynaptic Ca(2+) elevation and group I metabotropic glutamate receptor (I-mGluR) activation. Moreover, brief OMDM-188 treatments for several minutes were sufficient to suppress both DSI and the I-mGluR-induced retrograde eCB signalling in cultured hippocampal neurons. These results are consistent with the hypothesis that 2-AG for synaptic retrograde signalling is supplied as a result of on-demand biosynthesis by DGLα rather than mobilization from presumptive pre-formed pools.
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