Comparative actions of quisqualate and N-methyl-D-aspartate, excitatory amino acid agonists, on guinea-pig cochlear potentials.
We examined dose-dependent changes in the amplitude of guinea-pig cochlear microphonic potentials (CM), summating potentials (SP) and compound auditory nerve action potentials (CAP) produced after perfusing perilymphatic scalae with artificial perilymph containing either the transmitter candidate, L-glutamate; one of the excitatory amino acid agonists, quisqualate, kainate, N-methyl-D-aspartate (NMDA) or D-glutamate; or the control, alpha-ketoglutarate. None of these compounds significantly altered CM or SP. Kainate abolished CAP, but only partial suppression occurred using maximal effective doses of quisqualate (67%) or L-glutamate (82%). The remaining compounds had only marginal effects on CAP. The potency of quisqualate (EC50 = 14.8 microM) exceeded that of both kainate (EC50 = 66.9 microM) and L-glutamate (EC50 = 1.41 mM). These data suggest the presence of neuronal, possibly postsynaptic, excitatory amino acid receptor subpopulations which are preferentially sensitive to quisqualate and to kainate, but not to NMDA. These findings are discussed in the framework of our hypothesis that the proposed quisqualate and kainate receptors are normally activated by an endogenous excitatory amino acid such as L-glutamate which the hair cells release as a neurotransmitter.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006168:Guinea Pigs; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D000159:Vestibulocochlear Nerve / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D010069:Oxadiazoles; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D007608:Kainic Acid