Effects of Quinolinic and Kynurenic Acids on Central Neurons
Interest in the cellular basis of the actions of kynurenines in the central nervous system can be dated to 1981 when a range of cyclic analogs of the excitatory amino acids glutamate and aspartate were tested on the excitability of neurons in the cerebral cortex of anesthetised rats (Stone and Perkins, 1981; Stone, 1984). The earliest observations were of an excitatory action of quinolinic acid on cortical neurons, an action which clearly provided some explanation for the convulsant effects of quinolinic acid reported previously by Lapin and his colleagues (see Lapin, 1989). The excitation is summarized in histogram form in Fig. 1 which also reveals one of the major properties of quinolinic acid excitation also discovered in 1981. This is the sensitivity of the response to antagonism by compounds known to be active at the population of dicarboxylic amino acid receptors which show a preference for activation by N-methyl-D-aspartate (NMDA). Thus, in Fig. 1, the cell recorded in this case in the hippocampus in vivo was excited by applications of quinolinic acid, NMDA and quisqualic acid all applied by microiontophoresis from glass micropipettes on to a single neuron in the CA1 region of the hippocampal formation. The iontophoresis of 2-amino-5-phosphonopentanoic acid (2AP5) is then able to prevent excitation in response to both quinolinic acid and NMDA, the response to quisqualic acid being unchanged.
KeywordsNMDA Receptor Kainic Acid Quinolinic Acid Kynurenic Acid Ibotenic Acid
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