The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission
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Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGLalpha) and beta (DGLbeta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLalpha knockout mice, whereas the retrograde suppression was intact in DGLbeta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLalpha knockout brains, whereas the 2-AG content was normal in DGLbeta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLalpha, but not by DGLbeta, mediates retrograde suppression at central synapses.
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DAGL α and β transform diacylglycerols into 2-AG.
“In contrast, diacylglycerol lipase (DAGL) α and β transform diacylglycerols into 2-AG (Bisogno et al, 2003;Gao et al, 2010;Tanimura et al, 2010).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Tanimura et al, 2010
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- Authors
- Tanimura, A., Yamazaki, M., Hashimotodani, Y., Uchigashima, M., Kawata, S., Abe, M., Kita, Y., Hashimoto, K., Shimizu, T., Watanabe, M., Sakimura, K., & Kano, M.
- Affiliations
- The University of Tokyo (JP)
- Brain Research Institute, Niigata University (JP)
- Hokkaido University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Kano, Masanobu
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 65
- Issue
- 3
- Pages
- 320-327
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2116754069
- Cited by
- 472
- References
- 48
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 19 · 2023: 18 · 2022: 23 · 2021: 31 · 2020: 20 · 2019: 29 · 2018: 24 · 2017: 31 · 2016: 31 · 2015: 38 · 2014: 34 · 2013: 33 · 2012: 49
- FWCI
- 33.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- 2-arachidonoylglycerol, diacylglycerol lipase alpha, endocannabinoids, synaptic transmission, anandamide, cerebellum, hippocampus, striatum, central synapses
- MeSH terms
- Animals, Animals, Newborn, Arachidonic Acids, Calcium, Cells, Cultured, Cerebellum, Corpus Striatum, Electric Stimulation, Gene Expression Regulation, Glycerol, Hippocampus, Lipoprotein Lipase, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Neural Inhibition, Synaptic Transmission, Neurons, Potassium Chloride, Mice, Knockout, Patch-Clamp Techniques, Statistics, Nonparametric, Excitatory Postsynaptic Potentials, Mice, Polyunsaturated Alkamides, Inhibitory Postsynaptic Potentials, Endocannabinoids, In Vitro Techniques
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