Glutamate is the major excitatory neurotransmitter in the Central Nervous System (CNS) where its actions are mediated by different types of membrane receptors classified into "ionotropic" (iGluR) and "metabotropic" (mOluR) glutamate receptors (reviewed by Nakanishi, 1992). iGlu receptors (NMDA, N-methyl-D-aspartate; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and kainate receptors) form membrane ion channels permeable to mono- and divalent cations, and their activation is responsible for fast excitatory synaptic transmission; however, this class of receptors, particularly NMDA receptors, has been widely implicated in the pathophysiology of neuronal damage in most of acute and chronic neurodegenerative disorders (Choi, 1992; Doble, 1999). A sustained activation of NMDA receptors induces excessive and prolonged increases in intracellular free Ca2+ levels. Ca2+ activates a series of intracellular enzymes, including phospholipase A2, xanthine oxidase, and constitutive nitric oxide synthase, which in turn trigger a cascade of events leading to a form of cell death, termed "excitotoxicity" (Choi, 1992). mGlu receptors are coupled to G proteins and regulate the activity of a variety of membrane enzymes and ion channels (reviewed by Pin and Duvoisin, 1995). mGlu receptors form a family of eight subtypes, which are subdivided into three groups on the basis of sequence similarities and transduction pathways. Group-I includes mGlul and mGlu5 receptors, which are coupled to polyphosphoinositide (PPI) hydrolysis and can also regulate the activity of different types of K+ channels. Group-II (mGlu2 and mGlu3) and group-Ill (mGlu4, -6, -7, -8) receptors are negatively coupled to adenylate cyclase activity in heterologous expression systems and, with the exception of mGlu6 receptors, share the ability to modulate different types of voltage-sensitive Ca2+ channels when expressed in their native environment. Both iGlu and mGlu receptors have an estabHshed role in the CNS, and, in particular, mGlu receptors are involved in various aspects of CNS physiology and pathology, including modulation of excitatory synaptic transmission, developmental plasticity, learning and memory processes, and neurodegeneration (Nakanishi, 1994; Conn and Pin, 1997; Bruno et al 2001).
|Title of host publication||Glutamate Receptors in Peripheral Tissue: Excitatory Transmission Outside the CNS|
|Number of pages||7|
|ISBN (Print)||9780306486449, 0306479737, 9780306479731|
|Publication status||Published - 2005|
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