Molecular biology and ontogeny of glutamate receptors in the mammalian central nervous system

Timothy Simeone, Russell M. Sanchez, Jong M. Rho

Research output: Contribution to journalReview article

64 Citations (Scopus)

Abstract

Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic terminals, glutamate binds to both ionotropic and metabotropic receptors to mediate fast, slow, and persistent effects on synaptic transmission and integrity. There are three types of ionotropic glutamate receptors. N-Methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropfionic acid (AMPA), and kainate receptors are principally activated by the agonist bearing its name and are permeable to cationic flux; hence, their activation results in membrane depolarization. All ionotropic glutamate receptors are believed to be composed of four distinct subunits, each of which is topologically arranged with three transmembrane-spanning and one pore-lining (hairpin loop) domain. In contrast, metabotropic glutamate receptors are G protein (guanine nucleotide-binding protein) -coupled receptors linked to second-messenger systems. Group I metabotropic glutamate receptors are linked to phospholipase C, which results in phosphoinositide hydrolysis and release of calcium from intracellular stores. Group II and group III metabotropic glutamate receptors are negatively linked to adenylate cyclase, which catalyzes the production of cyclic adenosine monophosphate. Each metabotropic glutamate receptor is composed of seven transmembrane-spanning domains, similar to other members of the superfamily of metabotropic receptors, which includes noradrenergic, muscarinic acetylcholinergic, dopaminergic, serotonergic (except type 3 receptors), and γ-aminobutyric acid (GABA) type B receptors. This review summarizes the relevant molecular biology and ontogeny of glutamate receptors in the central nervous system and highlights some of the roles that they can play during brain development and in certain disease states.

Original languageEnglish
Pages (from-to)343-360
Number of pages18
JournalJournal of Child Neurology
Volume19
Issue number5
StatePublished - May 2004

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Metabotropic Glutamate Receptors
Glutamate Receptors
Molecular Biology
Central Nervous System
Ionotropic Glutamate Receptors
Glutamic Acid
GABA-B Receptors
Kainic Acid Receptors
AMPA Receptors
Guanine Nucleotides
Presynaptic Terminals
Type C Phospholipases
Second Messenger Systems
N-Methylaspartate
Phosphatidylinositols
GTP-Binding Proteins
Adenylyl Cyclases
Synaptic Transmission
Cyclic AMP
Cholinergic Agents

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

Cite this

Molecular biology and ontogeny of glutamate receptors in the mammalian central nervous system. / Simeone, Timothy; Sanchez, Russell M.; Rho, Jong M.

In: Journal of Child Neurology, Vol. 19, No. 5, 05.2004, p. 343-360.

Research output: Contribution to journalReview article

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