Neuropharmacological actions of kynurenic and quinolinic acids on horizontal cells of the isolated fish retina.
We have studied the effects of naturally occurring metabolites of tryptophan, kynurenic and quinolinic acids, on the electrophysiological responses of retinal horizontal cells in the fish (Rutilus rutilus, the roach). Quinolinic acid usually hyperpolarizes the cells and reduces their light evoked responses (S-potentials) but on occasion, it causes a slight depolarization of the membrane potential. These actions are similar to those found with N-methyl-D-aspartate (NMDA) and our results are consistent with the proposal that it acts at NMDA binding sites. Kynurenic acid (greater than or equal to mM) invariably hyperpolarizes horizontal cells to their potassium Nernst equilibrium potential and, more significantly, blocks the depolarizing actions exerted on them by excitatory amino acids, such as kainic and quisqualic acids. We show that this action persists in the presence of the synaptic blocker, cobalt chloride, and thus is not mediated by chemical synaptic activity. Kynurenic acid does not reverse depolarization of horizontal cells by dopamine or gamma-aminobutyric acid, thus its inhibitory effects are selective to the actions of excitatory amino acids. Neither xanthurenic acid, a close structural analogue of kynurenic acid, nor quinolinic acid are effective in blocking depolarizations by excitatory amino acids.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003530:Cyprinidae / Q000502:physiology*; D005074:Evoked Potentials, Visual / Q000187:drug effects; D007736:Kynurenic Acid / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D009474:Neurons / Q000145:classification* / Q000502:physiology; D010775:Photic Stimulation; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D012160:Retina / Q000166:cytology / Q000502:physiology*
D011725:Pyridines; D011805:Quinolinic Acids; D001224:Aspartic Acid; D003035:Cobalt; D016202:N-Methylaspartate; C018021:cobaltous chloride; D017378:Quinolinic Acid; D007736:Kynurenic Acid