Pittaluga A, Pattarini R, Severi P, Raiteri M
Istituto di Farmacologia e Farmacognosia, University of Genoa, Italy.
AIDS. 1996 May;10(5):463-8. doi: 10.1097/00002030-199605000-00003.
To investigate the effect of HIV-1 gp120 on the function of glutamate receptors of the N-methyl-D-aspartate (NMDA) type in the human brain.
The monitoring of neurotransmitter release from superfused isolated nerve endings is widely recognized as a technique appropriate for the study of neurotransmitter release and to attribute a precise localization to the site(s) of action of drugs able to modulate release.
Synaptosomes (pinched-off nerve endings) were prepared from fresh human brain tissue samples removed during neurosurgery, labelled with [3H]-noradrenaline and superfused at a rate of 0.5 ml/min with NMDA in the presence of gp41, gp160, gp120 or the V3 loop, with or without NMDA receptor antagonists. Fractions of superfusate were collected and measured for radioactivity.
NMDA elicited a glycine-sensitive release of [3H]-noradrenaline from human brain synaptosomes. HIV-1 gp120 potentiated the NMDA (1 mM)-evoked [3H]-noradrenaline release (maximal effect approximately 110% at 1 nM). The release elicited by NMDA plus gp120 was prevented by the classical NMDA receptor antagonists dizocilpine or 7-chlorokynurenic acid, as well as by memantine. The potentiation by gp120 of the NMDA-evoked [3H]-noradrenaline release was mimicked by gp160 but not by gp41. The effect of gp120 was retained by the V3 loop. Finally, gp120 reversed (1 nM) and surmounted (10nM) the antagonism by 10 microM 7-chlorokynurenate of the NMDA-evoked [3H]-noradrenaline release.
gp 120 binds directly through the V3 loop at noradrenergic axon terminals in human brain neocortex and may alter the function of presynaptic NMDA receptors mediating regulation of noradrenaline release.
研究人类免疫缺陷病毒1型糖蛋白120（HIV-1 gp120）对人脑N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体功能的影响。
监测从经超灌流的分离神经末梢释放神经递质，这一技术被广泛认为适用于研究神经递质释放，并能精确确定能够调节释放的药物的作用位点。
从神经外科手术中切除的新鲜人脑组织样本制备突触体（ pinched-off nerve endings），用[3H]-去甲肾上腺素标记，并在gp41、gp160、gp120或V3环存在的情况下，以0.5毫升/分钟的流速用NMDA进行超灌流，同时加入或不加入NMDA受体拮抗剂。收集超灌流液的部分并测量放射性。
NMDA引起人脑突触体中[3H]-去甲肾上腺素的甘氨酸敏感释放。HIV-1 gp120增强了NMDA（1毫摩尔）诱发的[3H]-去甲肾上腺素释放（在1纳摩尔时最大效应约为110%）。NMDA加gp120引起的释放被经典的NMDA受体拮抗剂地卓西平或7-氯犬尿氨酸以及美金刚阻断。gp160模拟了gp120对NMDA诱发的[3H]-去甲肾上腺素释放的增强作用，但gp41没有。V3环保留了gp120的作用。最后，gp120逆转（1纳摩尔）并克服（10纳摩尔）了10微摩尔7-氯犬尿酸对NMDA诱发的[3H]-去甲肾上腺素释放的拮抗作用。
gp120通过V3环直接与人脑新皮质中去甲肾上腺素能轴突终末结合，并可能改变介导去甲肾上腺素释放调节的突触前NMDA受体的功能。
