A Review of Glutamate Receptors I: Current Understanding of Their Biology

Abstract

Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

Effect of N-Methyl-D-Aspartate Receptor Antagonist on Radiation-Induced Gut Injuries in Mice

“…Acting on glutamate receptors (GluRs), it plays a key role in nearly all aspects of normal brain function including learning and memory, movement, cognition, development, and synaptic plasticity [6], [7]. GluRs are classified into two groups, ionotropic receptors (iGluRs) and metabotropic receptors (mGluRs).…”

Asymmetric Syntheses of Analogs of Kainic Acid

“…L-glutamic acid (Glu), one of 20 proteinogenic amino acids, possesses numerous functions as listed in Table 1 [Rousseaus, C. G. 2008]. Glu and its metabolism and function in the detoxification of ammonia in the brain, as well as its role as a building block in the synthesis of proteins and peptides, have been studied for decades.…”

“…Through both ligand-gated ion channels at ionotropic receptors (iGluRs) and at G protein-coupled metabotropic receptors (mGluRs), L-Glu activates its corresponding receptors, contributing to basal excitatory synaptic transmission. Therefore, it is an excitatory neurotransmitter [Rousseaus, C. G. 2008]. …”

“…Glu is estimated to mediate approximately 50% of all synaptic transmissions in the CNS and is involved in almost all aspects of normal brain function including learning, memory, movement, cognition, and development [Rousseaus, C. G. 2008].…”

“…However, Glu, Asp, and structurally similar compounds, such as domoic acid 9, can be neurotoxic when they excessively stimulate the same excitatory receptors, and this action is postulated to be involved in the pathogenesis of some types of acute and chronic insults to the CNS [Rousseaus, C. G. 2008] [Choi, D. W. 1995]. This excitotoxic effect can be significant during acute diseases such as ischemic stroke and trauma, or moderate but prolonged in such chronic neurodegenerative diseases as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis [Beal, M. F. 1995] [Starr, M. S. 1995] [Plaitakis, A. et al 1996] [Shaw, P. J. and Ince, P. G. 1997].…”