Journal
PHARMACOLOGICAL REVIEWS
Volume 73, Issue 4, Pages 298-487Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/pharmrev.120.000131
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Funding
- National Institutes of Health National Institute of Neurological Disorders and Stroke [NS097536, NS116055, NS088479, NS083660, NS107253, NS040701, NS105502, NS105804, NS113530, NS111619]
- National Institute of General Medical Sciences [GM103546]
- National Cancer Institute [CA206573]
- National Science Foundation [1818086]
- UK Research and Innovation [MC_U105174197]
- Biotechnology and Biological Sciences Research Council [BB/N002113/1]
- National Institutes of Health National Institutes of Health National Institute of Neurological Disorders and Stroke [NS111745, NS113632]
- National Institute of Mental Health [MH085926]
- Robertson funds at Cold Spring Harbor Laboratory
- Doug Fox Alzheimer's Fund
- Austin's Purpose, Heartfelt Wing Alzheimer's Fund
- Gertrude and Louis Feil Family Trust
- National University of Singapore [R184000261101]
- National Institutes of Health National Institute of Mental Health [MH123474]
- Intramural Research Program of the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Intramural Research Program of the National Institutes of Health National Institute of Neurologic Disorders and Stroke
- Canadian Institutes of Health Research [FRN 136832, FRN 142431, FRN 162317]
- National Institutes of Health National Institute of General Medical Sciences [GM122528]
- National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD082373]
- Janssen Research and Development
- Allergan
- Sage Therapeutics
- Biogen
- Janssen
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1818086] Funding Source: National Science Foundation
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This study summarizes the physiological effects of L-glutamate and the importance of ionotropic glutamate receptors in brain function. Research on iGluRs has advanced rapidly, particularly in areas such as receptor structure, function, pharmacology, and roles in neurophysiology.
Many physiologic effects of L-glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels are critical to brain function and are centrally implicated in numerous psychiatric and neurologic disorders. There are different classes of iGluRs with a variety of receptor subtypes in each class that play distinct roles in neuronal functions. The diversity in iGluR subtypes, with their unique functional properties and physiologic roles, has motivated a large number of studies. Our understanding of receptor subtypes has advanced considerably since the first iGluR subunit gene was cloned in 1989, and the research focus has expanded to encompass facets of biology that have been recently discovered and to exploit experimental paradigms made possible by technological advances. Here, we review insights from more than 3 decades of iGluR studies with an emphasis on the progress that has occurred in the past decade. We cover structure, function, pharmacology, roles in neurophysiology, and therapeutic implications for all classes of receptors assembled from the subunits encoded by the 18 ionotropic glutamate receptor genes. Significance Statement--Glutamate receptors play important roles in virtually all aspects of brain function and are either involved in mediating some clinical features of neurological disease or represent a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of this class of receptors will advance our understanding of many aspects of brain function at molecular, cellular, and system levels and provide new opportunities to treat patients.
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