Allosteric regulation of the N-methyl-D-aspartate receptor-linked ion channel complex and effects of ethanol in ethanol-withdrawal seizure-prone and -resistant mice.
The effects of ethanol, glycine, and spermidine on the specific binding of [3H]MK-801 were characterized in Triton-treated membranes prepared from the hippocampus and cortex of ethanol-withdrawal seizure-prone (WSP) and -resistant (WSR) mice. Glycine, an allosteric agonist at the NMDA receptor-linked ion channel complex, caused an increase in specific [3H]MK-801 binding to hippocampal membrane preparations. There were no significant differences in EC50 values between the selected lines for the effect of glycine (WSP, 391.7 +/- 48.4 nM; WSR, 313.4 +/- 77 nM) in the presence of 10 microM NMDA or in the maximal response to the agonist (WSP, 1.75 +/- 0.26 pmol/mg of protein; WSR, 1.67 +/- 0.22 pmol/mg of protein). The EC50 values for the spermidine-induced increase in [3H]MK-801 binding in membranes from hippocampus in the absence (WSP, 11.7 +/- 0.83 microM; WSR, 9.98 +/- 1.29 microM) or in the presence of 10 microM glycine and 10 microM NMDA (WSP, 2.1 +/- 0.35 microM; WSR, 2.37 +/- 0.42 microM) also did not differ. Similar results were obtained in cortical membranes. Saturation isotherms indicated that there was no difference in the density of [3H]MK-801 binding sites, or in their affinity for the radioligand, between the mouse lines. In addition, administration of ethanol by inhalation (24 h) to WSP and WSR mice did not cause an increase in the density of [3H]MK-801 binding sites, and there was no difference in the density or affinity of binding sites between the mouse lines.(ABSTRACT TRUNCATED AT 250 WORDS)
Carter
L A
LA
Research Service, Department of Veterans Affairs Medical Center, Portland, OR 97201.
Belknap
J K
JK
Crabbe
J C
JC
Janowsky
A
A
D000494:Allosteric Regulation; D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D016291:Dizocilpine Maleate / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D007473:Ion Channels / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013095:Spermidine / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*
D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D005998:Glycine; D013095:Spermidine