PHARMACOLOGICAL CHARACTERIZATION OF NON-NMDA SUBTYPES OF GLUTAMATE RECEPTOR IN THE NEONATAL RAT HEMISECTED SPINAL-CORD INVITRO

1 A grease-gap technique was used to record depolarizing responses to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) in the hemisected spinal cord of the neonatal rat. The pharmacology of non-NMDA subtypes of glutamate receptor was investigated with the novel quinoxalinedione, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)-quinoxaline (NBQX) and with a series of barbiturates. 2 NBQX antagonized AMPA- and kainate-, but not NMDA- induced depolarizations. The near parallel shifts of the major part of the dose-response curves for AMPA and kainate by NBQX gave pA2 values (+/- s.e.) of 6.7 +/- 0.2 and 6.8 +/- 0.2 respectively, consistent with a common site of action for these two agonists. 3 Below the 50% level at which these pA2 values were calculated, however, an NBQX-resistant plateau was seen within the kainate, but not the AMPA, dose-response curve. 4 In decreasing order of potency, methohexitone, secobarbitone, thiopentone, pentobarbitone and phenobarbitone preferentially reduced kainate-, rather than AMPA- and NMDA-, induced depolarizations. Methohexitone was also the most selective with IC50s against kainate, AMPA and NMDA of 31 +/- 7, 172 +/- 47 and > 200-mu-M respectively. 5 The NBQX-resistant plateau seen within the kainate dose-response curve was reduced by methohexitone. Kainate antagonism by methohexitone was not reduced by 50-mu-M picrotoxin. 6 We conclude that, while mixed agonist actions may hamper demonstration of antagonist selectivity, depolarizations induced by the non-NMDA ionotropic agonists, AMPA and kainate, are mediated in part via distinct receptors.