Role of Ca+2 and other second messengers in excitatory amino acid receptor mediated neurodegeneration: clinical perspectives.
Neurodegeneration associated with neurological disorders such as epilepsy, Huntington's Chorea, Alzheimer's disease, and olivoponto cerebellar atrophy or with energy failure such as ischemia, hypoxia, and hypoglycemia proceeds subsequent to overexposure of neurons to excitatory amino acids of which glutamate and aspartate may be quantitatively the most important. The toxic action of glutamate and aspartate is mediated through activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA subtypes. Antagonists for these receptors can act as neuroprotectants both in in vitro model systems (e.g., cultured neurons) and in vivo. Activation of receptors leads to an increase in the intracellular Ca++ concentration and also to an increase in other second messengers such as cGMP. Thus, Ca++ channel antagonists may have neuroprotective action under certain conditions.
Schousboe
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Dept. of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen, Denmark.
Belhage
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Frandsen
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000502:physiology*; D009410:Nerve Degeneration / Q000502:physiology*; D017459:Receptors, Amino Acid / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D017459:Receptors, Amino Acid; D002118:Calcium