ACTION OF THE NEUROTOXIN KAINIC ACID ON HIGH AFFINITY UPTAKE OF L-GLUTAMIC ACID IN RAT-BRAIN SLICES

Kainic acid is a linear competitive inhibitor (Kis 250 μm) 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 μm) 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. Copyright © 1979, Wiley Blackwell. All rights reserved