Kainic Acid: Insights into Its Receptor-Mediated Neurotoxic Mechanisms
Historically, kainic acid (KA) was selected as a potential exitotoxin because the evidence at the time was consistent with the notion that, as a conformationally restricted analogue of L-glutamate, it was a potent agonist at glutamate receptors (Olney et at., 1974; Coyle and Schwarcz, 1976). Since the first reports of the perikaryal-specific neurotoxic action of intracerebrally injected KA, it has become increasingly apparent that the mechanism of its neurotoxic effects is complex. Consequently, it has been our strategy for clarifying the mechanism of neurotoxicity of KA to focus on receptor specific interactions of the drug. We have felt that this approach might lead to a better understanding of the proximate physiologic events that result in perikaryal-specific neuronal degeneration. Furthermore, the effects of KA might be distinguished from other receptor-specific excitatory amino acid analogues (Watkins and Evans, 1981) such as N-methyl-D-aspartic acid (NMDA) and quisqualic acid as well as more generalized consequences of excessive stimulation of the broad class of the acidic amino acid receptors. These studies have provided evidence of the unique physiologic, pharmacologic and toxicologic properties associated with activation of receptors for KA.
KeywordsExcitatory Amino Acid Kainie Acid Domoic Acid Ibotenic Acid Cerebellar Slice
Unable to display preview. Download preview PDF.
- Curtis, D. and Johnston, G.A.R. (1974). Eben Physiol. 69, 97–188.Google Scholar
- Ferkany, J. W., Slevin, J.T., Zaczek, R. and Coyle, J.T. Neurobehavioral Toxicology, in press.Google Scholar
- Slevin, J., Collins, J., Lindsley, K. and Coyle, J.T. Brain Res., in press.Google Scholar
- Svedes, J.S., Sedo, R.J. and Atkinson, D.E. (1975) J. Biol. Chem., 250, 6930–6938.Google Scholar