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ACTIONS OF l ‐ AND d ‐HOMOCYSTEATE IN RAT CNS: A CORRELATION BETWEEN LOW‐AFFINITY UPTAKE AND THE TIME COURSES OF EXCITATION BY MICROELECTROPHORETICALLY APPLIED L‐GLUTAMATE ANALOGUES
Author(s) -
Cox D. W. G.,
Headley M. H.,
Watkins J. C.
Publication year - 1977
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.1471-4159.1977.tb10707.x
Subject(s) - amino acid , ouabain , biophysics , in vitro , chemistry , metabolism , biochemistry , biology , sodium , organic chemistry
— A correlation has been attempted between the uptake characteristics of l ‐ and d ‐homocysteate and the time courses of neuronal excitation by these and other amino acids related to l ‐glutamate. The uptake of l ‐ and d ‐homocysteate and of l ‐[ 35 S]homocysteate was studied in individual slices of rat cerebral cortex at 37°C. Tissue: medium ratios attained over l0 min for the unlabelled enantiomers at 2.5 mM were 3.7 for l ‐homocysteate but only 0.8 for the d ‐isomer. The uptake of l ‐[ 35 S]homocysteate over the concentration range 0.09 μ m ‐2 m m can be attributed mainly to a low‐affinity transport process with K m approx 3 m m and V max 1.7 μmol/g/min, but a high‐affinity process of low V max may make a minor contribution at the lower concentrations within this range. In terms of dependence on energy metabolism and [Na + ], and on inhibition by p‐chloromercuriphenylsulphonate, ouabain and structural analogues of the amino acid, the main uptake system for L‐[ 35 S]homocysteate appears to be similar to that mediating low‐affinity uptake of l ‐glutamate and other acidic amino acids. d ‐Homocysteate was but a weak inhibitor of this uptake system compared with other structural analogues. The time courses of excitation by 6 amino acids were determined by microelectrophoretic application to rat spinal neurones. d ‐Homocysteate induced responses with recovery times considerably longer than those of the other amino acids; this correlates with the absence of rapid uptake systems demonstrated for this amino acid in cortical tissue. d ‐Glutamate and l ‐homocysteate, which are only accumulated by low‐affinity transport mechanisms, induced responses with recovery periods similar to those of l ‐glutamate, l ‐aspartate and d ‐aspartate, which are accumulated by both high‐ and low‐affinity uptake systems. Although contributions of other factors to the observed time courses, such as rates of association and dissociation of the amino acid‐receptor complexes, cannot be excluded, the present results are consistent with the hypothesis that low‐affinity uptake systems of high V max play an important role in the rapid termination of the effects of amino acid excitants.