Ethanol sensitivity of recombinant human N-methyl-D-aspartate receptors.
In this study, the ethanol sensitivity of human N-methyl-D-aspartate (NMDA) receptors stably expressed in L(tk-) cells, or transiently expressed in HEK 293 cells and Xenopus oocytes was determined. NMDA receptor function was measured using fura-2 calcium imaging for L(tk-) cells, whole cell voltage-clamp for HEK 293 cells, and two-electrode voltage clamp for oocytes. Ethanol inhibited NMDA receptor function in all three expression system, but was less potent for receptors expressed in L(tk-) cells. NMDA receptors composed of NR1a/2B subunits were inhibited to a greater extent by ethanol than NR1a/2A receptors when expressed in L(tk-) cells and HEK 293 cells, but not in oocytes. These results suggest that the method of receptor expression and assay system used may influence the degree of ethanol inhibition of recombinant NMDA receptors.
Smothers
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CT
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Box 980524, Richmond, VA 23298, USA. csmother@hsc.vcu.edu
Clayton
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R
Blevins
T
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Woodward
J J
JJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007424:Intracellular Fluid; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014981:Xenopus
D002118:Calcium; D000431:Ethanol; D005456:Fluorescent Dyes; D016257:Fura-2; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor