Pharmacology and regional variations of quinolinic acid-evoked excitations in the rat central nervous system.
A physiological and pharmacological investigation of a novel endogenous excitant, quinolinic acid, was carried out in male rats using conventional iontophoretic techniques. It was established that quinolinic acid responses were preferentially reduced by antagonists acting at the N-methyl-D-aspartate (NMDA) preferring receptor, such as (+/-)-2-amino-7-phosphono-heptanoic acid and 1-hydroxy-3-amino-pyrrolidone-2. Glutamic acid diethyl ester reduced responses to quinolinic acid, quisqualic acid and NMDA with no clear specificity. Streptomycin, thought to act at the quisqualic acid receptor, largely spared quinolinic acid responses, being more effective against quisqualic acid evoked excitations. It is therefore suggested that quinolinic acid acts primarily at the NMDA receptor. In addition, the sensitivity of various components of the neuraxis to quinolinic acid was assessed and compared with glutamate and NMDA. Neurons in the spinal cord and cerebellum were largely unresponsive to quinolinate, whereas cells in the neocortex, striatum and hippocampus responded to this agonist to a similar degree as glutamate. In the cortex quinolinate was about one-fifth as active as NMDA, which together with quinolinic acid was much less active in the spinal cord and cerebellum. It is concluded that the possibility that quinolinic acid has a neurotransmitter type function at central "amino acid" receptors merits further investigation.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000378:metabolism; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism*
D005971:Glutamates; D010069:Oxadiazoles; D011725:Pyridines; D011760:Pyrrolidinones; D011805:Quinolinic Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; C011829:glutamic acid diethyl ester; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; C001369:1-hydroxy-3-amino-2-pyrrolidone; D017378:Quinolinic Acid