Any feedback?
Literature summary for 3.1.1.116 extracted from
- Brain regional cannabinoid CB1 receptor signalling and alternative enzymatic pathways for 2-arachidonoylglycerol generation in brain sections of diacylglycerol lipase deficient mice (2014), Eur. J. Pharm. Sci., 51, 87-95 .
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| glutathione | - |
Mus musculus |  |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | brain regional CB1 receptor-Gi/o-activity largely remains unaltered in DAGLalpha-knockout and DAGLb-knockout mice when compared to wild-type littermates. Following comprehensive pharmacological blockade of 2-AG hydrolysis, brain sections generate sufficient amounts of 2-AG to activate CB1 receptors throughout the regions endowed with these receptors. As demonstrated by LC/MS/MS, this pool of 2-AG is generated via tetrahydrolipstatin-sensitive enzymatic pathways distinct from DAGLalpha or DAGLbeta. Blockade of endocannabinoid hydrolysis by the irreversibly acting inhibitor MAFP evokes CP55,940-mimicking [35S]GTPgammaS binding responses throughout the CB1 receptor enriched brain regions of DAGLalpha-KO, DAGLbeta-KO, and WT mice brain sections. No statistically significant difference is observed in CP55,940-evoked regional CB1 receptor activity between DAGLb-KO and wild-type mice whereas in certain hippocampal regions of DAGLalpha-KO mice (hippocampus-overall, hippocampus-CA3 and hippocampus-dentate gyrus), sub-maximal concentrations of CP55,940 evoke a statistically significant increase in CB1 receptor activity. The observed labelling patterns evoked by both MAFP and CP55,940 are abolished with the CB1 receptor-selective antagonist AM251, confirming that responses are being mediated via the CB1 receptors. Comparison of 2-AG and anandamide (AEA, the other principal endocannabinoid) levels between unprocessed cryosections of DAGLalpha-KO, DAGLbeta-KO and wild-type mice brains | Mus musculus |
| additional information | brain regional CB1 receptor-Gi/o-activity largely remains unaltered in DAGLalpha-knockout and DAGLbeta-knockout mice when compared to wild-type littermates. Following comprehensive pharmacological blockade of 2-AG hydrolysis, brain sections generate sufficient amounts of 2-AG to activate CB1 receptors throughout the regions endowed with these receptors. As demonstrated by LC/MS/MS, this pool of 2-AG is generated via tetrahydrolipstatin-sensitive enzymatic pathways distinct from DAGLalpha or DAGLbeta. Blockade of endocannabinoid hydrolysis by the irreversibly acting inhibitor MAFP evokes CP55,940-mimicking [35S]GTPgammaS binding responses throughout the CB1 receptor enriched brain regions of DAGLalpha-KO, DAGLbeta-KO and WT mice brain sections. No statistically significant difference is observed in CP55,940-evoked regional CB1 receptor activity between DAGLb-KO and wild-type mice whereas in certain hippocampal regions of DAGLalpha-KO mice (hippocampus-overall, hippocampus-CA3, and hippocampus-dentate gyrus), sub-maximal concentrations of CP55,940 evoke a statistically significant increase in CB1 receptor activity. The observed labelling patterns evoked by both MAFP and CP55,940 are abolished with the CB1 receptor-selective antagonist AM251, confirming that responses are being mediated via the CB1 receptors. Comparison of 2-AG and anandamide (AEA, the other principal endocannabinoid) levels between unprocessed cryosections of DAGLalpha-KO, DAGLbeta-KO and wild-type mice brains | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| RHC 80267 | i.e. O,O'-[1,6-hexanediylbis(iminocarbonyl)]dioxime cyclohexanone or U 57908; i.e. O,O'-[1,6-hexanediylbis(iminocarbonyl)]dioxime cyclohexanone or U 57908 | Mus musculus | |
| tetrahydrolipstatin | THL; THL | Mus musculus | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | activates | Mus musculus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 1-acyl-2-arachidonoyl-sn-glycerol + H2O | Mus musculus | - |
2-arachidonoylglycerol + fatty acid | - |
? | |
| 1-acyl-2-arachidonoyl-sn-glycerol + H2O | Mus musculus | - |
2-arachidonoylglycerol + fatty acid | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mus musculus | Q6WQJ1 | - |
- |
| Mus musculus | Q91WC9 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Mus musculus | - |
| neuron | postsynaptic neurons | Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 1-acyl-2-arachidonoyl-sn-glycerol + H2O | - |
Mus musculus | 2-arachidonoylglycerol + fatty acid | - |
? | |
| 1-acyl-2-arachidonoyl-sn-glycerol + H2O | - |
Mus musculus | 2-arachidonoylglycerol + fatty acid | - |
r | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| DAGLalpha | - |
Mus musculus |
| DAGLbeta | - |
Mus musculus |
| diacylglycerol lipase | - |
Mus musculus |
| sn-1-specific lipase | - |
Mus musculus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 20 | - |
assay at | Mus musculus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Mus musculus |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | pharmacological elimination of 2-arachidonoylglycerol (2-AG) hydrolytic activity in rat brain sections leads to an accumulation of endogenous 2-AG and subsequent CB1 receptor activation. The brain regional CB1 receptor-Gi/o-activity largely remains unaltered in DAGLalpha-knockout and DAGLbeta-knockout mice when compared to wild-type littermates. Following comprehensive pharmacological blockade of 2-AG hydrolysis, brain sections generate sufficient amounts of 2-AG to activate CB1 receptors throughout the regions endowed with these receptors. As demonstrated by LC/MS/MS, this pool of 2-AG is generated via tetrahydrolipstatin-sensitive enzymatic pathways distinct from DAGLalpha or DAGLbeta. The DAGL activity generates 2-AG in sufficient amounts to activate CB1 receptors. The 2-AG accumulation is susceptible to two recognized inhibitors of the DAGLs, tetrahydrolipstatin (THL) and compound RHC80267 and CB1 receptor activity is modestly amplified by two DAGL activators, calcium and glutathione | Mus musculus |
| metabolism | the primary pathway for 2-arachidonoylglycerol (2-AG) generation is believed to be conversion from the diacylglycerols (DAGs) by two sn-1-specific lipases, DAGLalpha and DAGLbeta | Mus musculus |
| physiological function | endocannabinoids are the endogenous ligands of the G protein-coupled cannabinoid receptors. The principal brain endocannabinoid, 2-arachidonoylglycerol (2-AG), is enzymatically produced from the diacylglycerols (DAGs) by two sn-1-specific lipases, DAGLalpha and DAGLbeta, in postsynaptic neurons and then activates presynaptic CB1 receptors in a retrograde manner. DAGLalpha is the major enzyme needed for retrograde synaptic 2-AG signalling. In addition to the sn-1-specific DAGLs, additional 2-AG generating enzymatic pathways are active in brain sections | Mus musculus |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
