Excitatory amino acids: new tools for old stories or pharmacological subtypes of glutamate receptors: electrophysiological studies.
Although the N-methyl-D-aspartate (NMDA) subtype of L-glutamate receptor is well characterized, the significance of non-NMDA glutamate-sensitive binding sites is not well documented. In this study, a new tricyclic quinoxalinedione (NBQX) and an arthropod toxin (philanthotoxin) were shown to block responses of spinal neurones in vivo to kainate, quisqualate, and AMPA in parallel but had little effect on responses to NMDA. Philanthotoxin appeared to be a use-dependent antagonist consistent with a channel-blocking mode of action. On cortical wedges in vitro, however, NBQX proved to be a more potent antagonist of AMPA and quisqualate than of kainate (pA2 values of 7.1, 7.0, and 5.6, respectively) with no effect at 10 microM on responses to NMDA. These studies provide evidence that on cortical neurones, but not on spinal neurones. AMPA and kainate depolarize by pharmacologically different mechanisms.
Lodge
D
D
Department of Veterinary Basic Sciences, Royal Veterinary College, London, U.K.
Jones
M G
MG
Palmer
A J
AJ
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004594:Electrophysiology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011073:Polyamines; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D014862:Wasp Venoms / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D011073:Polyamines; D011810:Quinoxalines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D014862:Wasp Venoms; D007051:Ibotenic Acid; D016202:N-Methylaspartate; C034092:delta-philanthotoxin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid