6533b7d6fe1ef96bd1265e33
RESEARCH PRODUCT
Metabotropic glutamate receptors activate phospholipase D in astrocytes through a protein kinase C-dependent and Rho-independent pathway.
Elisabet SarriRaul PardoJ. Silvio GutkindFernando PicatosteChristoph Von Eichel-streiberRoser MasgrauJoan-marc Servitjasubject
rho GTP-Binding ProteinsIndolesBacterial ToxinsGlutamic AcidBiologyReceptors Metabotropic GlutamateSulfenic AcidsMaleimidesRats Sprague-DawleyCellular and Molecular NeuroscienceBacterial ProteinsStress FibersmedicinePhospholipase DAnimalsCysteineEgtazic AcidProtein kinase CCells CulturedProtein Kinase CChelating AgentsPharmacologyProtein Synthesis InhibitorsBrefeldin APhospholipase CDose-Response Relationship DrugEndothelin-1Phospholipase DADP-Ribosylation FactorsMetabotropic glutamate receptor 6Glutamate receptorDNAMolecular biologyRatsenzymes and coenzymes (carbohydrates)medicine.anatomical_structureMetabotropic receptorMetabotropic glutamate receptorAstrocytesType C PhospholipasesTetradecanoylphorbol Acetatelipids (amino acids peptides and proteins)Astrocytedescription
Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that mediate phospholipase D (PLD) activation in brain, but the mechanism underlying this response remains unclear. Here we used primary cultures of astrocytes as a cell model to explore the mechanism that links mGluRs to PLD. Glutamate activated both phospholipase C (PLC) and PLD with equal potency and this effect was mimicked by L-cysteinesulfinic acid, a putative neurotransmitter previously shown to activate mGluRs coupled to PLD, but not PLC, in adult brain. PLD activation by glutamate was dependent on Ca(2+) mobilization and fully blocked by both protein kinase C (PKC) inhibitors and PKC down-regulation, suggesting that PLD activation is secondary to PLC stimulation. Furthermore, brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) activation, partially inhibited the activation of PLD by glutamate. By contrast, pretreatment of astrocytes with Clostridium difficile toxin B, which inactivates small G proteins of the Rho family (Rho, Rac, and Cdc42), had no effect on PLD stimulation by glutamate. Taken together, these results indicate that PLD activation by mGluRs in astrocytes is dependent on PKC and small G proteins of the ARF family, but does not require Rho proteins.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-02-01 | Neuropharmacology |