Metabotropic glutamate receptors

Abstract

Metabotropic glutamate receptors (mGlus) are a family of G-protein-coupled receptors activated by the neurotransmitter glutamate. Molecular cloning has revealed eight different subtypes (mGlu1-8) with distinct molecular and pharmacological properties. Multiplicity in this receptor family is further generated through alternative splicing. mGlus activate a multitude of signalling pathways important for modulating neuronal excitability, synaptic plasticity and feedback regulation of neurotransmitter release. In this review, we summarize anatomical findings (from our work and that of other laboratories) describing their distribution in the central nervous system. Recent evidence regarding the localization of these receptors in peripheral tissues will also be examined. The distinct regional, cellular and subcellular distribution of mGlus in the brain will be discussed in view of their relationship to neurotransmitter release sites and of possible functional implications.

Microglial Activation in Stroke: Therapeutic Targets

“…100 -104 They also express all three groups of metabotropic receptors: group I (mGluR5), 105 group II (mGluR2 and 3), 106,107 and group III (mGluR4, 6, and 8). 106,108 Stimulation with either glutamate or with ionotropic glutamate receptor agonists induces microglial proliferation, morphological changes characteristic of microglial activation, and release of IL-1␤, TNF␣, NO, and ATP. 100,101,104,109 Conversely, activation of most mGluR types inhibits microglial inflammatory responses, 107,110 -112 with the exception that mGluR2 activation promotes microglial neurotoxicity.…”

Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

“…4,5 An imbalance of Glu concentration and loss of their corresponding receiving mGluR 5 in the synaptic cleft have been implicated in a number of CNS disorders, such as pain, anxiety, depression, Parkinson's disease, and addiction. 1, 4,6,7 The noninvasive imaging of the brain using a powerful technique such as magnetic resonance imaging (MRI) [high spatial resolution imaging (≤200 μm)] has revolutionized our understanding of the brain's organisational and operational complexity. 8 MR imaging procedures can be substantially improved when applied in combination with paramagnetic contrast agents (CAs) to enhance sensitivity and image quality.…”

Alternative splicing of G protein-coupled receptors: physiology and pathophysiology

“…In general, alternative splicing of GPCRs can lead to the expression of proteins with (see [58], CRH-Rs [92]). In many cases these proteins can bind their ligand, but do not transduce a signal, and thus behave as "decoy" receptors.…”

“…Although many members of the rhodopsin (family A) and frizzled/taste2 (frizzled and family C) sub-families are expressed as multiple isoforms, all members of the secretin (family B), adhesion (family B) and glutamate (family C) sub-families studied to date appear to undergo extensive alternative splicing due to their unique exon-intron organization [58,89,90]. A fascinating example of the importance of splicing in GPCR biology and hormone actions is the CRH-R1 receptor, which orchestrates mammalian responses to stressful stimuli [33].…”