Metabotropic glutamate receptor

About: Metabotropic glutamate receptor is a research topic. Over the lifetime, 9451 publications have been published within this topic receiving 587979 citations. The topic is also known as: GPCR_3_mtglu_rcpt & IPR000162.

The glutamate receptor ion channels

Abstract: The ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992 ([Hollmann and Heinemann, 1994][1]), stimulated this

Cloned Glutamate Receptors

Abstract: The application of molecular cloning technology to the study of the glutamate receptor system has led to an explosion of knowledge about the structure, expression, and function of this most important fast excitatory transmitter system in the mammalian brain. The first functional ionotropic glutamate receptor was cloned in 1989 (Hollmann et al 1989) , and the results of this molecular-based approach over the past three years are the focus of this review. We discuss the implications of and the new questions raised by this work-which is probably only a glance at this fascinating and complex signaling system found in brains from the snails to man. Glutamate receptors are found throughout the mammalian brain, where they constitute the major excitatory transmitter system. The longest-known and best-studied glutamate receptors are ligand-gated ion channels, also called ionotropic glutamate receptors , which are permeable to cations. They have traditionally been classified into three broad subtypes based upon pharmaco­ logical and electrophysiological data: a-amino-3-hydroxy-5-methyl-4isoxazole propionate (AMPA) receptors, kainate (KA) receptors , and N-methyl-D-aspartate (NMDA) receptors. Recently, however, a family of G protein-coupled glutamate receptors , which are also called metabotropic glutamate or transl -aminocyclopentanel ,3-dicarboxylate (tACPD) recep­ tors, was identified (Sugiyama et al 1987) . (For reviews of the classification and the pharmacological and electrophysiological properties of glutamate receptors see Mayer & Westbrook 1987, Collingridge & Lester 1989, Honore 1989, Monaghan et al 1989, Wroblewski & Danysz 1 989, Hansen &

Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory.

Abstract: Alzheimer's disease constitutes a rising threat to public health. Despite extensive research in cellular and animal models, identifying the pathogenic agent present in the human brain and showing that it confers key features of Alzheimer's disease has not been achieved. We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease. The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. Soluble Abeta from Alzheimer's disease brain also disrupted the memory of a learned behavior in normal rats. These various effects were specifically attributable to Abeta dimers. Mechanistically, metabotropic glutamate receptors were required for the LTD enhancement, and N-methyl D-aspartate receptors were required for the spine loss. Co-administering antibodies to the Abeta N-terminus prevented the LTP and LTD deficits, whereas antibodies to the midregion or C-terminus were less effective. Insoluble amyloid plaque cores from Alzheimer's disease cortex did not impair LTP unless they were first solubilized to release Abeta dimers, suggesting that plaque cores are largely inactive but sequester Abeta dimers that are synaptotoxic. We conclude that soluble Abeta oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.

Pharmacology and functions of metabotropic glutamate receptors.

Abstract: ▪ Abstract In the mid to late 1980s, studies were published that provided the first evidence for the existence of glutamate receptors that are not ligand-gated cation channels but are coupled to effector systems through GTP-binding proteins. Since those initial reports, tremendous progress has been made in characterizing these metabotropic glutamate receptors (mGluRs), including cloning and characterization of cDNA that encodes a family of eight mGluR subtypes, several of which have multiple splice variants. Also, tremendous progress has been made in developing new highly selective mGluR agonists and antagonists and toward determining the physiologic roles of the mGluRs in mammalian brain. These findings have exciting implications for drug development and suggest that the mGluRs provide a novel target for development of therepeutic agents that could have a significant impact on neuropharmacology.

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Abstract: The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.