Versus AMPA-Preferring Glutamate Receptors in DRG and Hippocampal Neurons
The Journal of Neuroscience, June 1994, 14(6): 38813897 Willardiines Differentiate Agonist Binding Sites for Kainate- versus AMPA-preferring Glutamate Receptors in DRG and Hippocampal Neurons Linda A. Wang,’ Mark L. Mayer,’ David E. Jane,2 and Jeffrey C. Watkins2 ‘Laboratory of Cellular and Molecular Neurophysiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892 and 2Department of Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 lTD, United Kingdom Concentration jump responses to 5substituted (S)-willar- [Key words: glutamate, kainate, AMPA, willardiine, desen- diines were recorded from dorsal root ganglion (DRG) and sitization, dose-response, dorsal root ganglion, hippocam- hippocampal neurons under voltage clamp. After block of PusI desensitization by concanavalin-A, dose-response analysis for activation of kainate-preferring receptors in DRG neurons Convincing evidence suggestingthe occurrence of a glutamate gave the potency sequence trifluoromethyl > iodo > bromo receptor subtype preferentially activated by kainic acid first came = chloro > nitro = cyano > kainate > methyl > fluoro > from studies on sensoryneuron axons in the dorsal root of the (R,S)-AMPA z+ willardiine; EC,, values for the most and least rat spinal cord (Agrawal and Evans, 1986). These experiments potent willardiine derivatives, 5trifluoromethyl (70 nM) and revealed quisqualate and AMPA to be 30 and 70 times less 5-fluoro (69 PM), differed 1 OOO-fold. The potency sequence potent than kainate; in contrast, for hippocampal neurons the for equilibrium responses at AMPA-preferring receptors in potency sequencefor these agonists is reversed, with (S’)-quis- hippocampal neurons was strikingly different from that ob- qualate and (R,S)-AMPA 160 and 13 times more potent than tained in DRG neurons: fluoro > cyano = trifluoromethyl = kainate (Patneau and Mayer, 1990).
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