Developmental decrease in ethanol inhibition of N-methyl-D-aspartate receptors in rat neocortical neurons: relation to the actions of ifenprodil.
Inhibition of N-methyl-D-aspartate (NMDA) receptor function by ethanol (EtOH) and interactions between EtOH and the noncompetitive NMDA receptor antagonist ifenprodil were examined in neocortical neurons from rat and human embryonic kidney (HEK) 293 cells expressing recombinant NMDA receptors. Ethanol inhibited receptor function at concentrations in the 10 to 100 mM range in cortical neurons. EtOH inhibition of NMDA receptor function decreased as a function of time in culture over a 4-wk period. No difference in EtOH inhibition of AMPA/kainate receptor function was observed in neurons from 2- to 4-wk-old cultures. The time course of decreased EtOH inhibition paralleled a developmental decrease in inhibition by the noncompetitive NMDA receptor antagonist ifenprodil in these cortical neurons. Inhibition by EtOH was decreased in magnitude in the presence of 10 microM ifenprodil in 2- to 3-wk-old cortical neurons, but not in 1-wk-old neurons. Ifenprodil inhibited the function of recombinant NMDA receptors expressed in HEK 293 cells. Consistent with earlier reports, ifenprodil selectively inhibited responses mediated by recombinant receptors containing the NMDAR2B subunit at concentrations up to 10 microM. EtOH also inhibited the function of recombinant NMDA receptors expressed in HEK 293 cells. The potency of EtOH for inhibiting responses differed slightly among receptors containing different R2 subunits, especially at low EtOH concentrations. Finally, ifenprodil did not alter the effect of EtOH on recombinant R2A or 2B-containing NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Lovinger
D M
DM
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee, USA.
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000431:Ethanol; C010739:ifenprodil