Quinolinic Acid: A Pathogen in Seizure Disorders?
Multiple lines of experimental evidence, exemplified in several chapters of this volume, point to a prominent if not necessarily causative involvement of brain N-methyl-D-aspartate (NMDA) receptors in seizure phenomena. At the present time, the situation is reminiscent of that encountered in schizophrenia research where it appears that dopamine receptors are ‘somehow’ involved in psychiatric symptomatology (Snyder et al., 1974). While the theoretical framework for studies in those two seemingly quite unrelated areas is thus remarkably similar, one considerable difference exists: there is no question as to the identity of the endogenous agonist of the dopamine receptor. In fact, the catecholamine has lent its name to the ’dopamine hypothesis’ of schizophrenia. In contrast, no endogenous NMDA-agonist of similar prominence has emerged, which could be generally accepted as a candidate for a pathogen in human epileptic disorders. Yet the characterization of such an endogenous compound is eminently relevant, given the non-endogenous nature of NMDA and the apparent non-selectivity of glutamate for the NMDA-subtype of excitatory amino acid receptors (Foster and Fagg, 1984). Here we will review the growing body of evidence suggesting that quinolinic acid (pyridine 2,3-dicarboxylic acid; QUIN) may fulfill such a role.
KeywordsTemporal Lobe Epilepsy Kainic Acid Quinolinic Acid Neuronal Cell Body Nicotinamide Adenine Dinucleotide
Unable to display preview. Download preview PDF.
- Foster, A.E., White, R.J., and Schwarcz, R., 1986, Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissuein vitro, J, Neurochem. in press.Google Scholar
- Gholson, R.K., Ueda, I., Ogasawara, N., and Henderson, L.M., 1964, The enzymatic conversion of quinolinate to nicotinic acid mononucleotide in mammalian liver, J, Biol. Chem.239:1208.Google Scholar
- Hauser, W.A., 1983, Status epilepticus: frequency, etiology, and neurological sequelae, in: Status Epilepticus: Mechanisms of Brain Damage and Treatment.A.V. Delgado-Escueta, C.G. Wasterlain, D.M. Treiman and R.J. Porter, eds., Raven Press, New York, p. 3.Google Scholar
- Henderson, L.M., and Ramasarma, G.B., 1949, Quinolinic acid metabolism. III. Formation from 3-hydroxyanthranilic acid by rat liver preparations, Biol. Chem. 181:687.Google Scholar
- Hsu, S.M., Raine, L., and Fanger, H., 1981, Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures, J. Histochem. Cytochem.29:557.Google Scholar
- Nadler, J.V., Evanson, D.A., and Cuthbertson, G.J., 1981, Comparative toxicity of kainic acid and other acidic amino acids toward rat hippocampal neurons, Neuroscience 6: 2505.Google Scholar
- Perkins, M.N., and Stone, T.W., 1983, Pharmacology and regional variations of quinolinic acid-evoked excitation in the rat central nervous system, J. Pharmacol. Exp .Therap.226:551.Google Scholar
- Schwarcz, R., and Köhler, C., 1983, Differential vulnerability of central neurons of the rat to quinolinic acid, Neurosci. Lett. 38:85.Google Scholar
- Schwarcz, R., Whetsell, W.O., Jr., and Mangano, R.M., 1983, Quinolinic acid: an endogenous metabolism that causes axon-sparing lesions in rat brain, Science 219: 316.Google Scholar
- Schwarcz, R., White, R.J., and Whetsell, W.O., Jr., 1985, 3-hydroxyanthranilic acid oxygenase: activity in lesioned rat striatum and in human brain tissue, Soo. Neurosci. Abstr. 11:240.6.Google Scholar
- Snyder, S.H., Banerjee, S.P., Yamamura, H.I., and Greenberg, D., 1974, Drugs, neurotransmitters and schizophrenia, Science 184: 1243.Google Scholar
- Wolfensberger, M., Amsler, U., Cuénod, M., Foster, A.C., Whetsell, W.O., Jr., and Schwarcz, R., 1983, Identification of quinolinic acid in rat and human brain tissue, Neurosci. Lett. 41:247.Google Scholar