Metabotropic glutamate receptors: Beyond the regulation of synaptic transmission

Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection

“…Specifically, glutamate and glutamate receptors may play a role in the induction of immune responses. T lymphocytes express glutamate receptors, including ionotropic AMPA receptors (52)(53)(54)(55)(56). Dendritic cells, the major cells responsible for antigen presentation, release glutamate when in contact with T cells (57), and T cells respond to low doses of glutamate with increased Ca 2ϩ influx, proliferation, migration, and adhesion (52, 53, 58, 59), suggesting an important role for glutamate in modulating the immune response (60).…”

Metabotropic Glutamate Receptors in Peripheral Tissues: Implications for Toxicology

“…Also, mGluR3 mRNA is increased by 5-fold in aldosterone-producing adenomas compared to normal human adrenal glands (Ye et al, 2007). Ectopic expression of mGluR1 in human normal melanocytes, which normally lack this receptor, resulted in melanocyte hyperproliferation and transformation into malignant tumors that set off distant metastases (Nicoletti et al, 2007;Marin & Chen, 2004). In the clinical setting, mGluR5 expression correlated with a decreased survival rate in patients with oral squamous cell carcinoma (Park et al, 2007) and an mGluR5 agonist increased tumor cell migration, invasion, and adhesion in human tongue cancer cells, an effect that was reversed by an mGluR5 antagonist (Park et al, 2007).…”

“…However, mGluRs have currently received much attention motivated by a strong belief in their potential as drug targets for treatment of anxiety disorders and schizophrenia (Lavreysen & Dautzenberg, 2008;Chaki et al, 2010;Mezler et al, 2010;Schlumberger et al, 2009;Moreno et al, 2009;Patil et al, 2007). The strongest suggestion that mGluRs are not exclusively synaptic receptors derives from numerous studies that demonstrate the presence of functional mGluRs in a number of peripheral non-neuronal cells, many of which do not even originate from the neural crest (Nicoletti et al, 2007), shifting the role of these receptors from mere synaptic regulators to modulators of basic cell functions (such as cell proliferation, differentiation and survival) and key mediators of peripheral tissue function and neuroendocrine events. Besides organs that receive direct glutamatergic innervations, such as the heart and the adrenal glands, peripheral mGluRs can be activated in the absence of synaptic glutamate because of the existence of a large metabolic glutamate pool into cells derived from the Krebs cycle (Nicoletti et al, 2007).…”

“…The strongest suggestion that mGluRs are not exclusively synaptic receptors derives from numerous studies that demonstrate the presence of functional mGluRs in a number of peripheral non-neuronal cells, many of which do not even originate from the neural crest (Nicoletti et al, 2007), shifting the role of these receptors from mere synaptic regulators to modulators of basic cell functions (such as cell proliferation, differentiation and survival) and key mediators of peripheral tissue function and neuroendocrine events. Besides organs that receive direct glutamatergic innervations, such as the heart and the adrenal glands, peripheral mGluRs can be activated in the absence of synaptic glutamate because of the existence of a large metabolic glutamate pool into cells derived from the Krebs cycle (Nicoletti et al, 2007). Then, metabolic glutamate can be transported outside the cell where it activates paracrine or autocrine mechanisms on cells expressing glutamate receptors.…”

Albuminuria and Glomerular Damage in Mice Lacking the Metabotropic Glutamate Receptor 1

“…15 Although most research in the mGlu receptors field has been "synaptically oriented," recent data extend the role of these receptors to other biological processes. Molecular analyses show functional expression of mGlu receptors in several nonneuronal cells, including bone, 16 testis, 17 and T cells, 18,19 indicating possible glutamate signaling in different systems (reviewed by Nicoletti and colleagues 20 ). At present, however, no data have been reported, to our knowledge, on a possible role in the kidney.…”