Kynurenic acid and quinolinic acid act at N-methyl-D-aspartate receptors in the rat hippocampus.
Responses evoked by several amino acid excitants, including the tryptophan metabolite quinolinic acid, were recorded intracellularly from CA1 pyramidal neurons in rat hippocampal slices. Quinolinate, N-methyl-D-aspartate (NMDA), ibotenate and (+/-)-cis-1-amino-1,3-dicarboxycyclopentane produced excitations characterized by burst firing of action potentials, tetrodotoxin-resistant spiking and apparent increases in input resistance measured with brief hyperpolarizing current pulses. L-Glutamate, kainate, quisqualate and (+/-)-2'-amino-3-hydroxy-5-methyl-4-isoxazole-3'-propionate depolarized CA1 pyramidal neurons and induced apparent decreases in input resistance. Quinolinate-, NMDA-, and ibotenate-induced focal depolarizations, but not L-glutamate, kainate- or quisqualate-induced responses, were strongly antagonized by specific NMDA receptor antagonists. The tryptophan metabolite kynurenic acid, at concentrations that antagonized focal depolarizations produced by NMDA, ibotenate and the endogenous excitant quinolinate, did not antagonize quisqualate or L-glutamate responses. In addition to its NMDA-type antagonist action, kynurenate blocked kainate-induced focal depolarizations.
Ganong
A H
AH
Cotman
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CW
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D011725:Pyridines; D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D017378:Quinolinic Acid; D007736:Kynurenic Acid; D007608:Kainic Acid