title: Alteration of [3H]MK-801 binding associated with the N-methyl-D-Aspartate receptor complex by acute ethanol in rat cortex and hippocampus in vitro.
abstract: We investigated the effect of ethanol on specific binding of [3H]MK-801 to the intrachannel phencyclidine (PCP) receptor site, as an index of change in the functional response of the N-methyl-D-Aspartate (NMDA)-associated ion channel. Saturation binding experiments were performed on synaptic membrane homogenates from adult rat cortex and hippocampus. [3H]MK-801 binding assays were conducted under conditions of basal, 10 microM glutamate, or 10 microM glutamate + 30 microM D-serine, with and without 50 or 100 mM ethanol. Association experiments of [3H]MK-801 binding (5 nM) were conducted under conditions of 0 or 10 microM glutamate, with varying concentrations of glycine (0.01, 0.10, and 10 microM) with and without 100 mM ethanol. Ethanol (50 and 100 mM) significantly decreased the percentage of high-affinity (open-channel state) MK-801 receptors with a concomitant increase in percentage of low-affinity receptors, but did not change high- and low-affinity constants of the two binding states. An ethanol-induced increase in the closed-channel receptor density in basal and activated conditions was suggested by the saturation experiments. Association experiments further explained this finding, in that ethanol (100 mM) significantly decreased fast component (open-channel) [3H]MK-801 binding in conditions of glycine (0.01-10 microM) only and activated conditions of glutamate + glycine (0.01-0.10 microM). However, the observed fast and slow kinetic rate constants of [3h]MK-801 binding, as well as total specific binding (fast + slow components), were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, 78713-7266, USA.
authors.forename: K
authors.initials: K
authors.lastname: Spuhler-Phillips
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez
authors.forename: P K
authors.initials: PK
authors.lastname: Randall
authors.forename: S W
authors.initials: SW
authors.lastname: Leslie
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D017478:Receptors, Phencyclidine / Q000187:drug effects / Q000502:physiology; D012694:Serine / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; D000431:Ethanol; D018698:Glutamic Acid; D012694:Serine; D016291:Dizocilpine Maleate; D005998:Glycine