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ACTION OF THE NEUROTOXIN KAINIC ACID ON HIGH AFFINITY UPTAKE OF l ‐GLUTAMIC ACID IN RAT BRAIN SLICES
Author(s) -
Johnston G. A. R.,
Kennedy Sue M. E.,
Twitchin B.
Publication year - 1979
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.1471-4159.1979.tb04518.x
Subject(s) - kainic acid , glutamic acid , quisqualic acid , aspartic acid , chemistry , biochemistry , convulsant , neurotoxin , binding site , amino acid , stereochemistry , receptor , glutamate receptor
Kainic acid is a linear competitive inhibitor ( K is 250 μ m ) of the ‘high affinity’ uptake of l ‐glutamic acid into rat brain slices. Kainic acid inhibits the ‘high affinity’ uptake of l ‐glutamic, d ‐aspartic and l ‐aspartic acids to a similar extent. Kainic acid is not actively taken up into rat brain slices and is thus not a substrate for the ‘high affinity’ acidic amino acid transport system or any other transport system in rat brain slices. Kainic acid (300 μ m ) does not influence the steady‐state release or potassium‐stimulated release of preloaded d ‐aspartic acid from rat brain slices. Kainic acid binds to rat brain membranes in the absence of sodium ions in a manner indicating binding to a population of receptor sites for l ‐glutamic acid. Only quisqualic and l ‐glutamic acid inhibit kainic acid binding in a potent manner. The affinity of kainic acid for these receptor sites appears to be some 4 orders of magnitude higher than for the ‘high affinity’ l ‐glutamic acid transport carrier. Dihydrokainic acid is approximately twice as potent as kainic acid as an inhibitor of ‘high affinity’ l ‐glutamic acid uptake but is some 500 times less potent as an inhibitor of kainic acid binding and at least 1000 times less potent as a convulsant of immature rats on intraperitoneal injection. Dihydrokainic acid might be useful as a ‘control uptake inhibitor’ for the effects of kainic acid on ‘high affinity’ l ‐glutamic acid uptake since it appears to have little action on excitatory receptors. N ‐Methyl‐ d ‐aspartic acid is a potent convulsant of immature rats, but does not inhibit kainic acid binding or ‘high affinity’ l ‐glutamic acid uptake. N ‐Methyl‐ d ‐aspartic acid might be useful as a ‘control excitant’ that activates different excitatory receptors to kainic acid and does not influence ‘high affinity’ l ‐glutamic acid uptake.