Metabotropic Glutamate Receptors
نویسندگان
چکیده
Metabotropic glutamate receptors (mGluR)s are G-protein-coupled receptors that function as modulators of synaptic function and glutamate transmission. Post-synaptically localized subtype 5 mGlu5 receptors are co-localized with adenosine A2a, dopamine, and N-methyl-D-aspartate (NMDA) receptors and regulate local protein synthesis and messenger RNA (mRNA) translation at synapses, and are thus ideally positioned to control synaptic plasticity. Aberrant synaptic plasticity appears to be involved in a number of developmental and degenerative neuropsychiatric disorders, including Parkinson’s disease. Pharmacological modulation of mGluR5 could potentially open new therapeutic avenues for the treatment of such disorders, for both symptomatic and neuroprotective purposes. In this review, we summarize a series of in vivo studies we performed in order to delineate the anatomical basis and functional role of mGluR5 antagonists in Parkinson’s disease models, taking advantage of high-resolution positron emission tomography (PET) and the recent development of novel specific radiopharmaceuticals. Our findings of a prevalent distribution of mGluR5 in the striatum and limbic structures and a significant binding enhancement following dopamine lesions support the role of mGlu5 receptors in modulating dopamineand glutamate-dependent signaling and synaptic plasticity within the basal ganglia cortico–subcortical loops.
منابع مشابه
(S)- 3,5-Dihydroxyphenylglycine )an agonist for group I metabotropic glutamate receptors( induced synaptic potentiation at excitatory synapses on fast spiking GABAergic cells in visual cortex
Introduction: (S)- 3,5-Dihydroxyphenylglycine (DHPG) is an agonist for group I metabotropic glutamate receptors. DHPG-induced synaptic depression of excitatory synapses on hippocampal pyramidal neurons is well known model for synaptic plasticity studies. The aim of the present study was to examine the effects of DHPG superfusion on excitatory synapses on pyramidal and fast-spiking GABAergic cel...
متن کاملMetabotropic glutamate receptors and their ligands applications in neurological and psychiatric disorders
Metabotropic glutamate receptors (mGluRs) consist of a large family of G-protein coupled receptors that are critical for regulating normal neuronal function in the central nervous system. The wide distribution and diverse physiological roles of various mGluR subtypes make them highly attractive targets for the treatment of a number of neurological and psychiatric disorders. The discovery of ...
متن کاملIonotropic Glutamate Receptors and their Role in Neurological Diseases
Glutamate is extensively and relatively uniformly distributed in the central nervous system (CNS) and its effects mediated by two distinct groups of receptors including Ionotropic and metabotropic glutamate receptors. Concentration of glutamate in the nervous system is much higher than in other tissues. Glutamate receptors play an important role in synaptic transmission, neural plasticity and n...
متن کاملP6: Metabotropic Glutamate Receptor-Dependent Role in the Formation of Long-Term Potentiation
Long-term potentiation (LTP) is a reflection of synaptic plasticity that induced by specific patterns of synaptic activity and has an important role in learning and memory. The first clue of the potential role of glutamate receptors in LTP was in 1991 with the observation that the mGluR agonists 1-amino-1, 3-cyclopentanedicarboxylic acid (ACPD), increased LTP. Studies have shown that ACPD induc...
متن کاملRegulation of NMDA Receptors by Metabotropic Glutamate Receptor 7
Background: The metabotropic glutamate receptors (mGluRs) are potential novel targets for mental disorders. Results: Activation of mGluR7 significantly reduced NMDAR-mediated currents and NMDAR surface expression via an actin-dependent mechanism. Conclusion: mGluR7, by affecting the cofilin/actin signaling, regulates NMDAR trafficking and function. Significance: It provides a potential mechanis...
متن کامل