GP120 CAN REVERT ANTAGONISM AT THE GLYCINE SITE OF NMDA RECEPTORS MEDIATING GABA RELEASE FROM CULTURED HIPPOCAMPAL-NEURONS

The effects of the human immunodeficiency virus type 1 envelope protei n gp120 on the release of GABA elicited bg N-methyl-D-aspartate (NMDA) from rat hippocampal neurons in primary culture has been investigated , NMDA (1-300 mu M) increased in a concentration-dependent manner (EC5 0 37.9 +/- 12 mu M) the release of [H-3]-GABA. The effect of 100 mu M NMDA was prevented by 30 mu M of the GABA transport inhibitor N-(4,4-d iphenyl-3-butenyl)guvacine (SKF 100330A), Glycine (10 mu M) Or gp120 ( 0.01 mu M) affected neither the basal nor the NMDA-evoked [H-3]-GABA r elease, The NMDA (100 mu M)-evoked release was prevented by 5,7-dichlo ro-kynurenic acid (5,7-DCKA), a selective antagonist at the glycine si te of the NMDA receptor, in a concentration-dependent manner (IC50 sim ilar or equal to 0.3 mu M). Glycine (3-10 mu M) or gp120 (0.003-0.01 m u M) produced reversal of the 5,7-DCKA antagonism in a way that sugges ted competition at a same site; gp120 was at least 3 orders of magnitu de more potent than glycine. It is suggested that gp120 may mimic glyc ine at NMDA receptors. (C) 1997 Wiley-Liss, Inc.