Comparison of ethanol sensitivity of rat brain kainate, DL-alpha-amino-3-hydroxy-5-methyl-4-isoxalone proprionic acid and N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
The effect of ethanol (EtOH) on kainate (KA), DL-alpha-amino-3-hydroxy-5-methyl-4-isoxalone proprionic acid and N-methyl-D-aspartate (NMDA) receptor-operated channels was examined electrophysiologically in Xenopus laevis oocytes expressing mRNA from rat hippocampus and cerebellum. EtOH (50, 100 mM) inhibited KA-induced currents but did not alter the EC50 for KA (approximately 78 microM). For a series of n-alcohols, potency for inhibition of KA responses was related to chain length. 6,7-dinitroquinoxaline-2,3-dione inhibited maximum KA responses with an IC50 of approximately 1 microM; EtOH (50, 100 mM) did not alter the IC50 for 6,7-dinitroquinoxaline-2,3-dione but did not produce further inhibition of KA-induced currents. Despite the apparent noncompetitive inhibition produced by EtOH on KA receptor-mediated responses, the EtOH inhibition increased as the KA concentration decreased in hippocampal and cerebellar mRNA expressing oocytes. This differential inhibition was not due to the different current amplitudes stimulated by low vs. high KA concentrations. In contrast, oocytes expressing NMDA channels demonstrated a constant percent inhibition by EtOH in the presence of 25 to 200 microM NMDA. Altering the extracellular Ca++ concentration did not affect the ability of EtOH to inhibit NMDA responses. Maximal NMDA-stimulated currents were inhibited by 100 mM EtOH to a lesser extent (31%) in oocytes injected with rat cerebellar mRNA than oocytes expressing rat hippocampal mRNA (47%), suggesting brain regional differences in NMDA channel inhibition by EtOH.(ABSTRACT TRUNCATED AT 250 WORDS)
Dildy-Mayfield
J E
JE
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
Harris
R A
RA
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D002118:Calcium; D000431:Ethanol; D007051:Ibotenic Acid; D007608:Kainic Acid; D016202:N-Methylaspartate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid