Stress-induced changes in adrenal neuropeptide Y expression are regulated by a negative feedback loop.
Stress-induced changes in adrenal neuropeptide Y expression are regulated by a negative feedback loop.
复制标题
压力引起的肾上腺神经肽 Y 表达变化受到负反馈环的调节。
DOI：
10.1111/jnc.12150
复制
发表时间：
2013
影响因子：
4.7
通讯作者：
Whim,MatthewD
中科院分区：
文献类型：
--
作者：
Wang,Qian;Whim,MatthewD
神经肽Y是由肾上腺髓质中的嗜铬细胞合成的共递质。在战斗或逃跑反应期间，这些细胞除了肾上腺素和去甲肾上腺素外还释放NPY。在应激诱导的反射后，NPY水平增加，作为调节儿茶酚胺能信号传导的稳态反应的一部分。在这里，我们研究了在小鼠短暂暴露于冷水强迫游泳试验后，NPY表达的控制。这种治疗导致两个群体的嗜铬细胞之间的NPY表达的转变，在1周的过程中逆转。当NPY（GFP）BAC转基因动物暴露于应激时，细胞质中非分泌性GFP增加，表明应激增加了NPY启动子活性。在体内，阻断Y2（而不是Y1或Y5）受体增加了基础肾上腺NPY表达，从而调节了应激的作用。我们的结论是，释放神经肽Y介导的负反馈回路，抑制其自身的表达。因此，NPY的水平由应激的增强作用和Y2受体的紧张性抑制作用之间的平衡决定。这可能是一种有效的方式，以确保这种调节剂的水平不会下降后，强烈的交感神经活动。
Neuropeptide Y is a co‐transmitter that is synthesized by chromaffin cells in the adrenal medulla. During the fight‐or‐flight response these cells release NPY in addition to epinephrine and norepinephrine. Following the stress‐induced reflex, the levels of NPY are increased as part of a homeostatic response that modulates catecholaminergic signaling. Here, we examined the control of NPY expression in mice after brief exposure to the cold water forced swim test. This treatment led to a shift in NPY expression between two populations of chromaffin cells that reversed over the course of 1 week. When NPY(GFP) BAC transgenic animals were exposed to stress, there was an increase in cytoplasmic, non‐secretable GFP, indicating that stress increased NPY promoter activity.In vivoblockage of Y2 (but not Y1 or Y5) receptors increased basal adrenal NPY expression and so modulated the effects of stress. We conclude that release of NPY mediates a negative feedback loop that inhibits its own expression. Thus, the levels of NPY are determined by a balance between the potentiating effects of stress and the tonic inhibitory actions of Y2 receptors. This may be an efficient way to ensure the levels of this modulator do not decline following intense sympathetic activity.