Quinolinic acid: a pathogen in seizure disorders?
The evidence for an involvement of QUIN in human seizure disorders is clearly circumstantial. Importantly, QUIN is not a classical neurotransmitter and may thus play only a negligible or no role at all in normal brain function (Foster et al., 1984). We have yet to understand if and how such a possibly inert metabolite may turn into a pathogen. Several crucial questions remain to be addressed before a case can be made for a 'quinolinic acid hypothesis' of temporal lobe epilepsy. Among the most prominent ones figure the extracellular concentration of QUIN in the human brain under normal and pathological ('epileptic') conditions, the relationship between QUIN metabolism in the brain and its extracellular concentration and, a related issue, the regulation of cerebral QUIN metabolism (i.e., turnover). It is of equal importance to assess if NMDA-receptors, particularly those in the hippocampus and other parts of the limbic system, can exert a modulatory function upon brain QUIN. Unquestionably, future experiments with selective NMDA-antagonists will prove useful for the elucidation of such possible (feedback) interactions.
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D002799:Cholinergic Fibers / Q000502:physiology; D003292:Convulsants; D004827:Epilepsy / Q000503:physiopathology*; D007608:Kainic Acid / Q000494:pharmacology; D008024:Ligands; D010088:Oxidoreductases / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D011725:Pyridines / Q000502:physiology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D003292:Convulsants; D008024:Ligands; D011725:Pyridines; D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D010088:Oxidoreductases; C026382:3-hydroxyanthranilic acid oxidase; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid; D007608:Kainic Acid