Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium Channel Blockers / pharmacology
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Cells, Cultured
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Dizocilpine Maleate / antagonists & inhibitors
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Dizocilpine Maleate / metabolism
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Electrophysiology
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HIV Envelope Protein gp120 / pharmacology*
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N-Methylaspartate / antagonists & inhibitors
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N-Methylaspartate / physiology
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N-Methylaspartate / poisoning
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Oocytes / metabolism
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Phencyclidine / analogs & derivatives
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Phencyclidine / antagonists & inhibitors
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Phencyclidine / metabolism
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Pipecolic Acids / antagonists & inhibitors
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Pipecolic Acids / metabolism
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Radioligand Assay
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Rats
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Receptors, N-Methyl-D-Aspartate / drug effects*
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Receptors, N-Methyl-D-Aspartate / metabolism
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Receptors, N-Methyl-D-Aspartate / physiology
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Recombinant Proteins
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Xenopus
Substances
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Calcium Channel Blockers
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HIV Envelope Protein gp120
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Pipecolic Acids
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Receptors, N-Methyl-D-Aspartate
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Recombinant Proteins
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selfotel
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N-Methylaspartate
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Dizocilpine Maleate
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tenocyclidine
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Phencyclidine