Sardo Pierangelo, Carletti Fabio, D'Agostino Stefania, Rizzo Valerio, Ferraro Giuseppe
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia umana, Università degli Studi di Palermo, Corso Tukory, 129-90134 Palermo, Italy.
Eur J Neurosci. 2006 Oct;24(7):1995-2002. doi: 10.1111/j.1460-9568.2006.05097.x. Epub 2006 Oct 16.
The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nomega-nitro-L-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission) were iontophoretically applied while performing single-unit extracellular recordings. The activity of most neurons was influenced in a statistically significant way: in particular, both current-related inhibitory L-NAME-induced effects (20/39 tested cells) and excitatory effects of SIN-1 (25/41 tested neurons), SNOG (19/32 tested cells) and 8-Br-cGMP (13/19 tested neurons) were demonstrated. Neither statistically significant differences between the responses of regularly and irregularly discharging cells, nor specific topographical clustering of responding neurons, were demonstrated. Neurons administered drugs oppositely modulating the NO neurotransmission often displayed responses to only one treatment. We hypothesize that NO neurotransmission could exert a modulatory influence upon subthalamic neurons, with a prevalent excitatory effect. However, in the light of the presence of some responses of opposite sign to the same drug displayed by different subthalamic neurons, more complex effects of NO neurotransmission could be suggested, probably due to interactions with other classical neurotransmitter systems.
在丘脑底核的许多细胞中已证实存在一氧化氮（NO）合酶和可溶性鸟苷酸环化酶，后者是主要的NO激活代谢途径。在本研究中，在麻醉大鼠中探索了通过微离子透入法给予改变NO神经传递的药物对96个丘脑底核神经元放电的影响。根据放电模式将记录的神经元分为规则放电和不规则放电两类。在进行单单位细胞外记录时，离子透入法应用了Nω-硝基-L-精氨酸甲酯（L-NAME；一种NO合酶抑制剂）、3-吗啉代-西多芬盐酸盐（SIN-1；一种NO供体）、S-亚硝基谷胱甘肽（SNOG；另一种NO供体）和8-溴-cGMP（cGMP的一种细胞可渗透类似物，是NO神经传递的主要第二信使）。大多数神经元的活动受到统计学上显著的影响：特别是，既证实了与电流相关的L-NAME诱导的抑制性效应（20/39个测试细胞），也证实了SIN-1（25/41个测试神经元）、SNOG（19/32个测试细胞）和8-溴-cGMP（13/19个测试神经元）的兴奋性效应。在规则放电和不规则放电细胞的反应之间未显示出统计学上的显著差异，也未显示出反应神经元的特定地形聚类。给予相反调节NO神经传递的药物的神经元通常仅对一种处理有反应。我们假设NO神经传递可能对丘脑底核神经元发挥调节作用，具有普遍的兴奋效应。然而，鉴于不同丘脑底核神经元对同一药物表现出一些相反符号的反应，可能提示NO神经传递有更复杂的效应，这可能是由于与其他经典神经递质系统的相互作用。
