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Excitatory Amino Acid Receptor Potency and Subclass Specificity of Sulfur‐Containing Amino Acids
Author(s) -
Pullan L. M.,
Olney J. W.,
Price M. T.,
Compton R. P.,
Hood W. F.,
Michel J.,
Monahan J. B.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb10024.x
Subject(s) - nmda receptor , amino acid , cysteine , chemistry , biochemistry , serine , kainate receptor , excitotoxicity , agonist , glutamate receptor , taurine , glycine , receptor , ampa receptor , enzyme
The sulfur‐containing amino acids, l ‐and d ‐cysteate, l ‐cysteine, l ‐and d ‐cysteine sulfinate, l ‐and d ‐cysteine‐S‐sulfate, l ‐cystine, l ‐and d ‐homocysteate, l ‐and d ‐homocysteine sulfinate, l ‐homocysteine, l ‐serine‐ O ‐sulfate, and taurine were tested in two excitatory amino acid receptor functional assays and in receptor binding assays designed to label specifically the AAl/ N ‐methyl‐ d ‐aspartate (NMDA), AA2/quisqualate, and AA3/kainate receptor recognition sites, as well as a CaCla‐dependent l ‐2‐amino‐4‐phosphonobutanoate site, and a putative glutamate uptake site. Agonist efficacies were determined by chick retinal excitotoxicity and stimulated sodium efflux from rat brain slices. d ‐Homocysteine sulfinate, l ‐homocysteate, and l ‐serine‐ O ‐sulfate had affinities most selective for the NMDA binding site, whereas the binding affinities of d ‐cysteate, d ‐cysteine sulfinate, d ‐homocysteate, and l ‐homocysteine sulfinate were less selective. However, the correlation of agonist activity sensitive to blockade by d ‐2‐amino‐7‐phosphonoheptanoate or d ‐2‐amino‐5‐phosphonopentanoate in the functional assays with affinity in the NMDA binding assay ( r = 0.87, p < 0.005 and r = 0.98, p < 0.005 for excitotoxicity and sodium efflux, respectively) allows characterization of these sulfur‐containing amino acids as acting at NMDA subclass receptors. l ‐Homocysteate, which has been found in the brain, and l ‐serine‐ O ‐sulfate are selective agonists and could serve as endogenous neurotransmitters at the NMDA receptor.