The envelope glycoprotein of HIV-1 alters NMDA receptor function.
Human immunodeficiency virus (HIV-1) infection often results in central nervous system (CNS) dysfunction, yet the mechanism(s) of action for HIV-1 in the CNS are not fully understood. In the present study gp120, the HIV-1 envelope glycoprotein, was shown to selectively inhibit N-methyl-D-aspartate (NMDA) receptor function. In addition to inhibiting radioligand binding to rat NMDA receptors, gp120 inhibited NMDA-induced currents in Xenopus oocytes, attenuated NMDA-stimulated calcium flux and cytotoxicity in cultured cerebellar granule cells, and provided partial protection against NMDA-induced lethality in vivo. These findings suggest that NMDA receptor complex is a possible site of action of HIV-1 within the CNS.
Sweetnam
P M
PM
NovaScreen, A Division of Nova Pharmaceutical Corporation, Baltimore, MD 21224.
Saab
O H
OH
Wroblewski
J T
JT
Price
C H
CH
Karbon
E W
EW
Ferkany
J W
JW
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000378:metabolism; D004594:Electrophysiology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000502:physiology / Q000506:poisoning; D009865:Oocytes / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D010875:Pipecolic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins; D014981:Xenopus
D002121:Calcium Channel Blockers; D015699:HIV Envelope Protein gp120; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C053672:selfotel; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine