Quisqualic acid induced sensitization and the active uptake of L-quisqualic acid by hippocampal slices.
Hippocampal CA1 pyramidal cell neurons are sensitized to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4) following exposure to L-quisqualic acid (QUIS). It has been proposed that induction of this 'QUIS-effect' involves uptake of L-QUIS by hippocampal cells. We have used o-phthaldialdehyde (OPA) derivatization and high performance liquid chromatographic (HPLC) separation of extracts from hippocampal slices which have been exposed to varied concentrations of L-QUIS to investigate L-QUIS uptake into hippocampal slices. We observe uptake rates such that the internal concentration of L-QUIS exceeds the bath concentration within 7 min. The fact that this uptake is concentrative indicates that it is mediated by an active transport system. In addition, uptake of L-QUIS may be linked to the induction of the QUIS-effect. At low concentrations of L-QUIS (< 4 microM), the QUIS-effect is only partially induced within the 4 min incubation time which maximally induces the effect when 16 microM L-QUIS is used. However, repeated 4 min exposure periods of slices to low L-QUIS concentrations will eventually induce the QUIS-effect even when each exposure is separated by extensive washout periods. Hence induction is dependent on both concentration and total exposure time. We also examined the effects of L-alpha-aminoadipic acid and L-serine-O-sulfate on the rate of L-QUIS uptake. Exposure of slices to these compounds prior to treatment with L-QUIS will block the physiological effects of L-QUIS. We found that these 'pre-blocking' compounds did not decrease the rate of L-QUIS uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Schulte
M K
MK
Department of Biochemistry, Medical School, University of Minnesota, Minneapolis 55455.
Roon
R J
RJ
Koerner
J F
JF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D016318:Quisqualic Acid / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects; D009764:o-Phthalaldehyde
D000613:Aminobutyrates; D015074:2-Aminoadipic Acid; D009764:o-Phthalaldehyde; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; C012729:2-amino-4-phosphonobutyric acid