ArticleMolecular bioSystems2010
Characterization of mice lacking candidate N-acyl ethanolamine biosynthetic enzymes provides evidence for multiple pathways that contribute to endocannabinoid production in vivo.
Article in Molecular bioSystems, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 132 citations in OpenAlex.
- Endocannabinoid and Opioid System Interactions in Exercise-Induced Hypoalgesia.Pain medicine (Malden, Mass.) · 2018Trial
- Distribution and subacute modulation of endocannabinoid metabolizing enzymes in the trigeminal complex and midbrain in a pre-clinical model of post-traumatic headache.The journal of headache and pain · 2026Article
- The influence of genetics on the endocannabinoid system gene expression and relevance for targeting reproductive conditions.Journal of cannabis research · 2025Article
- Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Expression of the endocannabinoid system and response to cannabinoid components by the human fetal testis.BMC medicine · 2023Article
- Gene expression of the endocannabinoid system in endometrium through menstrual cycle.Scientific reports · 2022Article
- Selective measurement of NAPE-PLD activity via a PLAJournal of lipid research · 2022Article
- Hypothalamic endocannabinoids in obesity: an old story with new challenges.Cellular and molecular life sciences : CMLS · 2021Review
- Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer.Cancers · 2021Review
- The role of endocannabinoids in consolidation, retrieval, reconsolidation, and extinction of fear memory.Pharmacological reports : PR · 2021Review
- Biosynthesis ofInternational journal of molecular sciences · 2020Article
- Glycerophosphodiesterase 3 (GDE3) is a lysophosphatidylinositol-specific ectophospholipase C acting as an endocannabinoid signaling switch.The Journal of biological chemistry · 2020Article
- Targeting the endocannabinoid system: a predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies.The EPMA journal · 2020Review
- Symmetrically substituted dichlorophenes inhibitThe Journal of biological chemistry · 2020Article
- Article
- Druggable Targets in Endocannabinoid Signaling.Advances in experimental medicine and biology · 2020Review
- Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues.Cellular and molecular life sciences : CMLS · 2019Review
- Canine NAPEPLD-associated models of human myelin disorders.Scientific reports · 2018Article
- The Endocannabinoid System and Heart Disease: The Role of Cannabinoid Receptor Type 2.Cardiovascular & hematological disorders drug targets · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The biosynthesis of the endocannabinoid anandamide (AEA) and related N-acyl ethanolamine (NAE) lipids is complex and appears to involve multiple pathways, including: (1) direct release of NAEs from N-acyl phosphatidyl ethanolamine (NAPE) precursors by the phosphodiesterase NAPE-PLD, and (2) double O-deacylation of NAPEs followed by phosphodiester bond hydrolysis of the resulting glycero-phospho (GP)-NAEs. We recently identified GDE1 as a GP-NAE phosphodiesterase that may be involved in the second pathway. Here, we report the generation and characterization of GDE1(-/-) mice, which are viable and overtly normal in their cage behavior. Brain homogenates from GDE1(-/-) mice exhibit a near-complete loss of detectable GP-NAE phosphodiesterase activity; however, bulk brain levels of AEA and other NAEs were unaltered in these animals. To address the possibility of compensatory pathways, we generated GDE1(-/-)/NAPE-PLD(-/-) mice. Conversion of NAPE to NAE was virtually undetectable in brain homogenates from these animals as measured under standard assay conditions, but again, bulk changes in brain NAEs were not observed. Interestingly, significant reductions in the accumulation of brain NAEs, including anandamide, were detected in GDE1(-/-)/NAPE-PLD(-/-) mice treated with a fatty acid amide hydrolase (FAAH) inhibitor that blocks NAE degradation. Finally, we determined that primary neurons from GDE1(-/-)/NAPE-PLD(-/-) mice can convert NAPEs to NAEs by a pathway that is not preserved following cell homogenization. In summary, combined inactivation of GDE1 and NAPE-PLD results in partial disruption of NAE biosynthesis, while also pointing to the existence of an additional enzymatic pathway(s) that converts NAPEs to NAEs. Characterization of this pathway should provide clarity on the multifaceted nature of NAE biosynthesis.
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