Suppression of ictal-like activity by kynurenic acid does not correlate with its efficacy as an NMDA receptor antagonist.
The involvement of excitatory amino acid (EAA) receptors in ictal-like activity was investigated using hippocampal slices from immature rats. Bath application of kynurenic acid (KYN) suppressed penicillin-induced synchronized afterdischarges. An identical concentration of D(-)2-amino-5-phosphonovaleric acid (D(-)AP5) spared the afterdischarges. Intracellular recordings confirmed D(-)AP5 to be the more potent N-methyl-D-aspartate antagonist. KYN's suppression of afterdischarges could not be clearly attributed to blockade of either kainate or quisqualate receptors. Thus, a novel kynurenate-preferring EAA receptor may play an important role in seizure generation in immature hippocampus.
Brady
R J
RJ
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Swann
J W
JW
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D010406:Penicillins; D016318:Quisqualic Acid; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D010069:Oxadiazoles; D010406:Penicillins; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D007736:Kynurenic Acid; D014633:Valine; D007608:Kainic Acid