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 protein gp120 on the release of GABA elicited by N-methyl-D-aspartate (NMDA) from rat hippocampal neurons in primary culture has been investigated. NMDA (1-300 microM) increased in a concentration-dependent manner (EC50 =37.9+/-12 microM) the release of [3H]-GABA. The effect of 100 microM NMDA was prevented by 30 microM of the GABA transport inhibitor N-(4,4-diphenyl-3-butenyl)guvacine (SKF 100330A). Glycine (10 microM) or gp120 (0.01 microM) affected neither the basal nor the NMDA-evoked [3H]-GABA release. The NMDA (100 microM)-evoked release was prevented by 5,7-dichloro-kynurenic acid (5,7-DCKA), a selective antagonist at the glycine site of the NMDA receptor, in a concentration-dependent manner (IC50 approximately 0.3 microM). Glycine (3-10 microM) or gp120 (0.003-0.01 microM) produced reversal of the 5,7-DCKA antagonism in a way that suggested competition at a same site; gp120 was at least 3 orders of magnitude more potent than glycine. It is suggested that gp120 may mimic glycine at NMDA receptors.
Fontana
G
G
Institute of Pharmacology and Pharmacognosy, University of Genoa, Italy.
Valenti
L
L
Raiteri
M
M
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D005998:Glycine / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1; D006624:Hippocampus / Q000166:cytology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000821:virology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D015699:HIV Envelope Protein gp120; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine