Cross-desensitization Reveals Pharmacological Specificity of Excitatory Amino Acid Receptors in Isolated Hippocampal Neurons

Ionic currents elicited by excitatory amino acids were studied, using the concentration clamp method, in enzymatically isolated rat hippocampal neurons. Cross‐desensitization between the responses to various agonists was applied to separate the activity of two types of receptors, N‐methyl‐D‐aspartate (NMDA) and non‐NMDA. NMDA receptors were selectively activated by NMDA, L‐ and D‐aspartate, D‐glutamate and quinolinate. Kainate and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate appeared to be selective, and quisqualate relatively less selective non‐NMDA agonists, acting on the same receptor type. L‐Glutamate, L‐ and D‐homocysteate activated both receptor types. It is supposed that two receptor sites, activation site and densensitization site, control the action of agonists at the non‐NMDA receptor. When examined in the cross‐desensitization experiments, NMDA and non‐NMDA receptors appear to be represented by the two homogeneous and independent receptor populations operating different ionic channels.