Kainic acid: insights into excitatory mechanisms causing selective neuronal degeneration.

Kainic acid, an acidic pyrolidine isolated from the seaweed Digenea simplex, is the most potent of the commonly used exogenous excitotoxins. The neurotoxic threshold of kainic acid is nearly two magnitudes lower than that of the other receptor-specific agonists, N-methyl-D-aspartic acid and quisqualic acid. Neurophysiological and ligand-binding studies indicate that the neurotoxic action of kainic acid is mediated by a specific receptor which exhibits a remarkably broad phylogenetic distribution in the nervous system of vertebrates and invertebrates. The mechanism of neurotoxicity of kainic acid appears to be indirect and requires the functional integrity of excitatory afferents to vulnerable neurons. Consistent with the excitotoxin hypothesis, kainic acid depletes high-energy phosphates and glucose at sites of neurotoxic action; nevertheless, the proximate cause of neurotoxicity may involve increases in intraneuronal calcium levels and the activation of calcium-dependent proteases. Kainic acid neurotoxicity provides a useful animal model for selective neuronal vulnerability that may shed light on the pathophysiology of a number of neurodegenerative disorders, including Huntington's disease and temporal lobe epilepsy.