TY - JOUR T1 - Ionotropic Glutamate Receptors: Regulation by G-protein Coupled Receptors JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.083352 SP - mol.112.083352 AU - Asheebo Rojas AU - Raymond Dingledine Y1 - 2013/01/24 UR - http://molpharm.aspetjournals.org/content/early/2013/01/24/mol.112.083352.abstract N2 - The function of many ion channels is under dynamic control by coincident activation of G protein - coupled receptors (GPCRs), particularly those coupled to the Gα-s and Gα-q family members. Such regulation is typically dependent upon the subunit composition of the ionotropic receptor or channel as well as the GPCR subtype and the cell-specific panoply of signaling pathways available. Because GPCRs and ion channels are so highly represented among targets of FDA-approved drugs, functional cross-talk between these drug target classes is likely to underlie many therapeutic and adverse effects of marketed drugs. GPCRs engage a myriad of signaling pathways that involve protein kinases A and C and, through PKC and interaction with β-arrestin, src kinase and hence the MAP kinase cascades. We focus here on the control of ionotropic glutamate receptor function by GPCR signaling because this form of regulation can influence the strength of synaptic plasticity. The amino acid residues phosphorylated by specific kinases have been securely identified in many ionotropic glutamate receptor subunits, but which of these sites are GPCR targets is less well known even when the kinase has been identified. NMDA, AMPA and heteromeric kainate receptors are all downstream targets of GPCR signaling pathways. The details of GPCR-iGluR cross-talk should inform a better understanding of how synaptic transmission is regulated and lead to new therapeutic strategies for neuropsychiatric disorders. ER -