Iwasaki Yusaku, Nakabayashi Hajime, Kakei Masafumi, Shimizu Hiroyuki, Mori Masatomo, Yada Toshihiko
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 320-0498, Japan.
Biochem Biophys Res Commun. 2009 Dec 18;390(3):958-62. doi: 10.1016/j.bbrc.2009.10.085. Epub 2009 Oct 21.
Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed in the brain and several peripheral tissues including the stomach and pancreas. Peripheral, as well as intracerebroventricular, administration of nesfatin-1 suppresses feeding behavior, though underlying mechanisms are unknown. In this study, we examined effects of nesfatin-1 on cytosolic Ca(2+) concentration (Ca(2+)) in the neurons isolated from the vagal afferent nodose ganglion of mice. Nesfatin-1 at 10(-10)-10(-8)M increased Ca(2+) in the isolated neurons in a concentration-dependent manner, and at 10(-8)M it increased Ca(2+) in 33 out of 263 (12.5%) neurons. These responses were inhibited under Ca(2+)-free conditions and by N-type Ca(2+) channel blocker, omega-conotoxin GVIA. All the nesfatin-1-responsive neurons also exhibited Ca(2+) responses to capsaicin and cholecystokinin-8. These results provide direct evidence that nesfatin-1 activates vagal afferent neurons by stimulating Ca(2+) influx through N-type channels, demonstrating the machinery through which peripheral nesfatin-1 can convey signals to the brain.
由核结合蛋白2加工而成的Nesfatin-1是一种厌食肽，在大脑以及包括胃和胰腺在内的多个外周组织中表达。外周给予以及脑室内给予Nesfatin-1均可抑制摄食行为，但其潜在机制尚不清楚。在本研究中，我们检测了Nesfatin-1对从小鼠迷走神经传入结状神经节分离出的神经元胞质Ca(2+)浓度（[Ca(2+)]i）的影响。10(-10)-10(-8)M的Nesfatin-1以浓度依赖的方式增加分离神经元中的[Ca(2+)]i，在10(-8)M时，263个神经元中有33个（12.5%）的[Ca(2+)]i增加。这些反应在无Ca(2+)条件下以及N型Ca(2+)通道阻滞剂ω-芋螺毒素GVIA作用下受到抑制。所有对Nesfatin-1有反应的神经元对辣椒素和胆囊收缩素-8也表现出[Ca(2+)]i反应。这些结果提供了直接证据，表明Nesfatin-1通过刺激Ca(2+)通过N型通道内流来激活迷走神经传入神经元，证明了外周Nesfatin-1向大脑传递信号的机制。
