GLUTAMATE AND CYSTEINYLGLYCINE EFFECTS ON NMDA RECEPTORS - INHIBITIONBY ETHANOL

Glutamate, the endogenous neurotransmitter at the NMDA receptor, and c ysteinylglycine are formed as byproducts of glutathione (GSH) metaboli sm by gamma-glutamyltranspeptidase. Glutamate and cysteinylglycine wer e investigated in Fura-2-loaded whole-brain neonatal (< 24 h) dissocia ted neurons to determine 1) if cysteinylglycine might act as a glycine site coagonist, 2) the inhibitory effects of ethanol on glutamate-sti mulated 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) (EC(50) = 0.7 mu M) in these cells was highly specific for NMDA receptor-operated calcium channels as they were dep endent on extracellular calcium, enhanced by glycine, and blocked by m agnesium, 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 inh ibitory sensitivity of ethanol to Glu-[Ca2+](i).