Cui Qiao-Ling, Yung Wing-Ho, Chen Lei
Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao, 266071 Shandong, China.
Neurosci Res. 2008 Feb;60(2):162-9. doi: 10.1016/j.neures.2007.10.007. Epub 2007 Oct 30.
Substance P is an important neurotransmitter or neuromodulator in central nervous system. Morphological studies have revealed the existence of substance P and its high affinity receptor, neurokinin-1 receptor, in globus pallidus. The expression of neurokinin-1 receptor in external globus pallidus has been reported to be decreased or unchanged in parkinsonian patients. To further investigate the effects of pallidal neurokinin-1 receptor in Parkinson's disease, an in vivo extracellular recording in 6-hydroxydopamine parkinsonian rats was performed. Micro-pressure ejection of selective neurokinin-1 receptor agonist, [Sar9,Met(O2)11] substance P (0.1mM), increased the spontaneous firing rate of pallidal neurons by 9.1% on the lesioned side, which was significantly weaker than that on the unlesioned side (20.7%), and that in normal rats (30.0%). The selective neurokinin-1 receptor antagonist, SR140333B, prevented the excitatory effects induced by [Sar9,Met(O2)11] substance P. Based on the action of substance P in globus pallidus of parkinsonian rats we hypothesize that the activity of neurokinin-1 receptors in globus pallidus may be decreased under parkinsonian state. This finding may provide a rationale for further investigations into the potential of pallidal substance P system in the treatment of Parkinson's disease.
P物质是中枢神经系统中一种重要的神经递质或神经调质。形态学研究已揭示苍白球中存在P物质及其高亲和力受体——神经激肽-1受体。据报道，帕金森病患者外侧苍白球中神经激肽-1受体的表达降低或未改变。为了进一步研究苍白球神经激肽-1受体在帕金森病中的作用，对6-羟基多巴胺帕金森病大鼠进行了体内细胞外记录。微量压力注射选择性神经激肽-1受体激动剂[Sar9,Met(O2)11]P物质（0.1mM），使损伤侧苍白球神经元的自发放电率增加了9.1%，明显弱于未损伤侧（20.7%）和正常大鼠（30.0%）。选择性神经激肽-1受体拮抗剂SR140333B可阻止[Sar9,Met(O2)11]P物质诱导的兴奋作用。基于P物质在帕金森病大鼠苍白球中的作用，我们推测帕金森病状态下苍白球中神经激肽-1受体的活性可能降低。这一发现可能为进一步研究苍白球P物质系统在帕金森病治疗中的潜力提供理论依据。
