Hu Man-Li, Zhang Wen-Wen, Cao Hong, Zhang Yu-Qiu
Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, Shanghai, 200032, China; Institutes of Integrative Medicine, Fudan University, 200032, China.
Neurosci Lett. 2019 Jan 23;692:16-22. doi: 10.1016/j.neulet.2018.10.049. Epub 2018 Oct 23.
cAMP (Cyclic Adenosine monophosphate), one of the most highly studied second messengers, is regulated by a family of adenylyl cyclase (AC) enzymes. Type 3 adenylyl cyclase (abbreviated as AC3), a subtype of adenylyl cyclase, is reported to be expressed in cilia in the olfactory and central nervous system and plays an important role in many physiological functions such as olfaction, development. However, expression of AC3 in the dorsal root ganglion (DRG) is not reported. In the present study, using immunohistochemical method, we discovered that AC3 immunoreactivity (IR) is predominantly expressed in the cytoplasm of small to medium sized DRG neurons. Double labelling revealed that the majority of AC3 IR are colocalized with CGRP (a peptidergic nociceptor marker), rarely with NF200 (a myelinated neuronal marker) or IB4 (a nonpeptidergic nociceptor marker). Furthermore, dense AC3 IR exists in the superficial dorsal horn, especially in laminaⅠand dorsal part of lamina II, where CGRP-positive DRG neurons terminate. The expression pattern of AC3 is similar between C57/BL6 J mouse and Sprague Dawley rat. For instance, AC3 is primarily expressed in the cell bodies of small to medium sized DRG neurons and the majority of AC3 IR is also in CGRP-containing neurons in rat. Taken together, our data suggest that AC3 is primarily expressed in the small to medium sized cell bodies and central terminals of CGRP-positive DRG neurons, implying AC3 enzyme might potentially function in nociception.
环磷酸腺苷（cAMP）是研究最为深入的第二信使之一，由腺苷酸环化酶（AC）家族调控。Ⅲ型腺苷酸环化酶（简称为AC3）是腺苷酸环化酶的一种亚型，据报道在嗅觉和中枢神经系统的纤毛中表达，并在嗅觉、发育等多种生理功能中发挥重要作用。然而，尚未见关于AC3在背根神经节（DRG）中表达的报道。在本研究中，我们采用免疫组化方法发现，AC3免疫反应性（IR）主要表达于中小尺寸DRG神经元的细胞质中。双重标记显示，大多数AC3 IR与降钙素基因相关肽（CGRP，一种肽能伤害性感受器标志物）共定位，很少与神经丝蛋白200（NF200，一种有髓神经元标志物）或IB4（一种非肽能伤害性感受器标志物）共定位。此外，在浅表背角，尤其是Ⅰ层和Ⅱ层背侧部分存在密集的AC3 IR，CGRP阳性DRG神经元在此处终止。C57/BL6 J小鼠和Sprague Dawley大鼠的AC3表达模式相似。例如，AC3主要在大鼠中小尺寸DRG神经元的细胞体中表达，并且大多数AC3 IR也存在于含CGRP的神经元中。综上所述，我们的数据表明，AC3主要在CGRP阳性DRG神经元的中小尺寸细胞体和中枢终末中表达，这意味着AC3酶可能在伤害感受中发挥作用。
