Endogenous glycine modulates N-methyl-D-aspartate-evoked release of adenosine and [3H]noradrenaline from rat cortical slices.
Strychnine-insensitive, glycinergic modulation of N-methyl-D-aspartate (NMDA)-evoked adenosine and [3H]noradrenaline release was investigated in superfused rat cortical slices. 7-Chlorokynurenic acid (100 microM) significantly decreased 300 microM NMDA-evoked adenosine and [3H]noradrenaline release. The addition of exogenous glycine (100 microM) reversed 7-chlorokynurenic acid antagonism. Higher concentrations of NMDA (500 microM, 3 mM) overcame the 7-chlorokynurenic acid (100 microM) block of NMDA-evoked adenosine release but not the block of NMDA-evoked [3H]noradrenaline release. Addition of exogenous glycine (100 microM) alone did not augment either adenosine or [3H]noradrenaline release. Addition of exogenous glycine show that endogenous glycine, acting at a strychnine-insensitive glycine site on the NMDA receptor, is required for NMDA receptor-mediated release of adenosine and noradrenaline. The finding that non-competitive block of NMDA-evoked adenosine release by 7-chlorokynurenic acid could be overcome by high NMDA concentrations supports the suggestion that spare NMDA receptors exist for adenosine release. Furthermore, heterogeneous endogenous glycine concentrations within the cortical slices cannot account for the observation that NMDA is 33 times more potent at releasing adenosine than at releasing [3H]noradrenaline.
Craig
C G
CG
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
White
T D
TD
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005998:Glycine / Q000502:physiology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007736:Kynurenic Acid; D013331:Strychnine; D000241:Adenosine; C057013:7-chlorokynurenic acid; D005998:Glycine; D009638:Norepinephrine