title: Inhibitors of diacylglycerol metabolism reduce time to the onset of glutamate release potentation by mGlu7 receptors.
abstract: At nerve terminals G protein coupled receptors modulate neurotransmitter release probability. We recently showed that prolonged activation of metabotropic glutamate receptor 7, mGlu7 receptor, potentiates glutamate release. This signalling involves phospholipase C activation via a pertussis toxin insensitive G protein, the hydrolysis of phosphatidylinositol (4,5)-bisphosphate, and the subsequent activation of the non-kinase diacylglycerol binding protein Munc13-1 which primes synaptic vesicle for exocytosis at the active zone. Here we found that inhibitors of diacylglycerol metabolism (diacylglycerol kinase inhibitor II and diacylglycerol lipase inhibitor RHC80267) remarkably reduce the time of mGlu7 receptor stimulation required for glutamate release potentiation in mice cerebrocortical nerve terminals. We conclude that changes in diacylglycerol levels at nerve terminals control the efficiency of the exocytotic release machinery.
authors: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain.
authors: José Javier
authors: JJ
authors: Ferrero
authors: Magdalena
authors: M
authors: Torres
authors: José
authors: J
authors: Sánchez-Prieto
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors*; D004075:Diglycerides / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D003512:Cyclohexanones; D004075:Diglycerides; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D018698:Glutamic Acid; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D019852:Diacylglycerol Kinase