Salt T E, Zhang H, Mayer B, Benz B, Binns K E, Do K Q
Department of Visual Science, Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
Eur J Neurosci. 2000 Nov;12(11):3919-25. doi: 10.1046/j.1460-9568.2000.00285.x.
S-nitroso-cysteinyl-glycine, a novel nitric oxide-adduct thiol compound, can be detected in the brain (2.3+/-0.6 pmol/mg protein), and released following stimulation of sensory afferents to the rat ventrobasal thalamus in vivo (resting conditions 17 nM; stimulation: 186 nM). Iontophoretic application of CysNOGly (20-80 nA) onto thalamic neurons in vivo resulted in enhancements of excitatory responses to either NMDA or AMPA (182+/-13.6% and 244+/-27.8% of control values, n = 15). CysNOGly enhanced responses to stimulation of vibrissal afferents to 132+/-2.2% (n = 7) of control values. In contrast, the dipeptide CysGly reduced responses of ventrobasal neurons to NMDA and AMPA (54+/-8.4% and 55+/-10.8% of control, n = 5). CysNOGly was also a potent activator of soluble guanylate cyclase in vitro. Moreover, we found that NMDA elevated CysNOGly levels in vitro and this stimulatory effect was reduced by inhibitors of the neuronal NO synthase and of the gamma-glutamyl transpeptidase, suggesting that production of NO and CysGly is a prelude to CysNOGly synthesis. These findings suggest that the nitrosothiol CysNOGly plays a role in synaptic transmission in the ventrobasal thalamus. We propose a novel synaptic buffering mechanism where S-nitroso-cysteinyl-glycine serves to restrict the locus of action of nitric oxide and so increase its local availability for target delivery. This could lead to a change in neuronal responses favouring sensory transmission similar to that seen in wakefulness or arousal in order to locally enhance transmission of persistent sensory stimuli.
S-亚硝基-半胱氨酰甘氨酸是一种新型一氧化氮加合物硫醇化合物，可在大脑中检测到（2.3±0.6皮摩尔/毫克蛋白质），并且在体内刺激大鼠腹侧基底丘脑的感觉传入神经后会释放出来（静息状态下为17纳摩尔；刺激后为186纳摩尔）。在体内对丘脑神经元进行CysNOGly（20 - 80纳安）的离子电泳应用，导致对NMDA或AMPA的兴奋性反应增强（分别为对照值的182±13.6%和244±27.8%，n = 15）。CysNOGly将对触须传入神经刺激的反应增强至对照值的132±2.2%（n = 7）。相比之下，二肽CysGly降低了腹侧基底神经元对NMDA和AMPA的反应（分别为对照值的54±8.4%和55±10.8%，n = 5）。CysNOGly在体外也是可溶性鸟苷酸环化酶的有效激活剂。此外，我们发现NMDA在体外可提高CysNOGly水平，并且这种刺激作用会被神经元型一氧化氮合酶抑制剂和γ-谷氨酰转肽酶抑制剂所降低，这表明一氧化氮和半胱氨酰甘氨酸的产生是CysNOGly合成的前奏。这些发现表明亚硝基硫醇CysNOGly在腹侧基底丘脑的突触传递中起作用。我们提出了一种新的突触缓冲机制，其中S-亚硝基-半胱氨酰甘氨酸用于限制一氧化氮的作用位点，从而增加其向靶标的局部可用性。这可能导致神经元反应发生变化，有利于类似于清醒或觉醒时所见的感觉传递，以便在局部增强持续性感觉刺激的传递。
