DIFFERENTIAL MODULATION BY CYCLOTHIAZIDE AND CONCANAVALIN-A OF DESENSITIZATION AT NATIVE LPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONICACID-PREFERRING AND KAINATE-PREFERRING GLUTAMATE RECEPTORS

Concanavalin A, cyclothiazide, and aniracetam, ligands that modulate d esensitization at glutamate receptors, were tested for their actions o n responses at kainate-preferring receptors in dorsal root ganglion (D RG) neurons and at lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring receptors in hippocampal neurons. In DRG neuron s concanavalin A blocked desensitization produced by either kainate or 5-chlorowillardiine and strongly potentiated the peak amplitude of re sponses to both agonists. However, in hippocampal neurons concanavalin A produced only weak potentiation of responses to kainate and 5-chlor owillardiine, and after treatment with lectin responses to 5-chlorowil lardiine remained strongly desensitizing. In contrast, cyclothiazide c ompletely blocked desensitization produced by 5-chlorowillardiine in h ippocampal neurons and strongly potentiated responses to kainate; the action of aniracetam was similar but much weaker. In DRG neurons cyclo thiazide and aniracetam had no effect on desensitization and instead p roduced weak inhibition of responses to kainate. The different sensiti vities of native AMPA- and kainate-preferring glutamate receptors to c yclothiazide and concanavalin A should prove useful for the differenti ation of glutamate receptor subtypes in other areas of the central ner vous system.