HIV-1 envelope protein gp120 potentiates NMDA-evoked noradrenaline release by a direct action at rat hippocampal and cortical noradrenergic nerve endings.
Exposure of rat or human neocortical or hippocampal tissue to glutamate receptor agonists elicits as Ca(2+)-dependent, exocytotic-like release of previously accumulated [3H]noradrenaline through activation of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors colocalized on the noradrenergic axon terminals. Here we show that the NMDA (100 microM)-evoked release of [3H]noradrenaline from superfused thin layers of isolated rat hippocampal or cortical nerve endings was potentiated when the human immunodeficiency virus type 1 coat protein gp120 was added to the superfusion medium concomitantly with NMDA. The effect of gp120 (10 pM to 3 nM) on the 100 microM NMDA-evoked release of [3H]noradrenaline was concentration-dependent; the maximal effect (approximately 140% potentiation) was reached at 100 pM of gp120. The protein was inactive on its own. The [3H]noradrenaline release evoked by NMDA (100 microM)+gp120 (100 pM) was prevented by classical NMDA receptor antagonists, as well as by 10 microM memantine. Neither the release evoked by NMDA nor that elicited by NMDA+gp120 was sensitive to the nitric oxide synthase inhibitor NG-nitro-L-arginine, suggesting no involvement of nitric oxide. The [3H]noradrenaline release elicited by 100 microM AMPA was unaffected by gp120. The protein potentiated the release evoked by 100 microM glutamate; the effect of 100 pM gp120 was quantitatively identical to that of 1 microM glycine, with no apparent additivity between gp120 and glycine. The antagonism by 1 microM 7-chloro-kynurenic acid of the NMDA-induced [3H]noradrenaline release was reversed by glycine or gp120.(ABSTRACT TRUNCATED AT 250 WORDS)
Pittaluga
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A
Istituto di Farmacologia e Farmacognosia, Genova, Italy.
Raiteri
M
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D018698:Glutamic Acid / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D009638:Norepinephrine