Glutamate and cysteinylglycine effects on NMDA receptors: inhibition by ethanol.
Glutamate, the endogenous neurotransmitter at the NMDA receptor, and cysteinylglycine are formed as byproducts of glutathione (GSH) metabolism by gamma-glutamyltranspeptidase. Glutamate and cysteinylglycine were investigated in Fura-2-loaded whole-brain neonatal (< 24 h) dissociated neurons to determine 1) if cysteinylglycine might act as a glycine site coagonist, 2) the inhibitory effects of ethanol on glutamate-stimulated increases in cytosolic calcium concentration (Glu-[Ca2+]i), and 3) the effects of cysteinylglycine on ethanol's inhibition of Glu-[Ca2+]i. Glu-[Ca2+]i (EC50 = 0.7 microM) in these cells was highly specific for NMDA receptor-operated calcium channels as they were dependent on extracellular calcium, enhanced by glycine, and blocked by magnesium, APV, and ethanol. However, because cysteinylglycine did not potentiate Glu-[Ca2+]i nor reverse ethanol inhibition of Glu-[Ca2+]i, it does not appear to act as a glycine coagonist or change the inhibitory sensitivity of ethanol to Glu-[Ca2+]i.
Morris
J
J
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712-1074, USA.
Leslie
S W
SW
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004151:Dipeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D016257:Fura-2; D018698:Glutamic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013050:Spectrometry, Fluorescence
D002492:Central Nervous System Depressants; D004151:Dipeptides; D016194:Receptors, N-Methyl-D-Aspartate; C028505:cysteinylglycine; D000431:Ethanol; D018698:Glutamic Acid; D002118:Calcium; D016257:Fura-2