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Science/Engineering Essentials of Toxic Chemical Risk: Science and Society
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Science/Engineering Excitatory Amino Acids - Clinical Results with Antagonists
Posted on 2010-07-22
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The excitatory effect of glutamate and aspartate on central nervous system neurons described in the early 1960s (Curtis and Watkins, 1960; Krnjevic and Phillis, 1963) initiated a massive research effort aimed at proving these compounds as important neurotransmitters. During the 1980s, glutamate gained the status of the major excitatory neurotransmitter in the brain. Receptors were classified as N-methyl-Daspartate (NMDA) and non-NMDA receptors, based on electrophysiological studies (Hicks et al., 1978; Davies et al., 1979; Watkins and Evans, 1981; McLennan and Liu, 1982). NMDA receptors are stimulated most potently by NMDA itself. Currents activated by NMDA receptors are carried by Na § K § and Ca 2§ (Dingledine, 1983; MacDermott et al., 1986). The non-NMDA receptors were later divided into three groups, t~- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, kainate receptors, and metabotropic glutamate receptors, based on the preferred agonists, AMPA, kainate, and glutamate (for a review, see Watkins et al., 1990). AMPA and kainate receptors are ion channel coupled mainly Na § channels, whereas metabotropic glutamate receptors mediate responses via G-protein-coupled second messengers.
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