机构：[1]Eye Institute in Eye & ENT Hospital, and NHC Key Laboratory of Myopia, Fudan University, China[2]Shanghai Key Laboratory of Visual Impairment and Restoration, China[3]Key Laboratory of Myopia, Chinese Academy of Medical Sciences, China[4]Department of Physiology and Pathophysiology, Fudan University School of Basic Medical Sciences, China[5]Department of Nursing, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China[6]Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
As an imidazoline I1 receptor agonist with very weak binding affinity for alpha(2)-adrenoceptors, moxonidine is commonly used in the treatment of hypertension. Moxonidine also has been implicated to act centrally to reduce airway vagal outflow. However, it is unknown at which central sites moxonidine acts to affect airway vagal activity, and how moxonidine takes effect at synaptic and receptor levels. In this study, airway vagal preganglionic neurons (AVPNs) were retrogradely labeled in neonatal rats from the intrathoracic trachea; retrogradely labeled AVPNs in the external formation of the nucleus ambiguus (NA) were identified in rhythmically active medullary slices using whole-cell patch-clamp techniques; and the effects of moxonidine on the spontaneous excitatory postsynaptic currents (EPSCs) of AVPNs were observed at synaptic level. The results show that moxonidine (10 mu mol.L-1) significantly inhibited the frequency of spontaneous EPSCs in both inspiratory-activated and inspiratory-inhibited AVPNs. This effect was partially blocked by SKF-86466 (10 mu mol.L-1), a highly selective antagonist of alpha(2)-adrenoceptors, or AGN-192403, a selective antagonist of imidazoline I1 receptors, and was completely blocked by efaroxan (10 mu mol.L-1), an antagonist of both alpha(2)-adrenoceptors and imidazoline I1 receptors. These results demonstrate that moxonidine inhibits the excitatory inputs to AVPNs via activation of both alpha(2)-adrenoceptors and imidazoline I1 receptors, and suggest that physiologically both of these two types of receptors are involved in the central regulation of airway vagal activity at preganglionic level. Moxonidine might be potentially useful in diseases with aberrant airway vagal activity such as asthma and chronic obstructive diseases.
基金：
NSFC (National Natural Science Foundation of China)National Natural Science Foundation of China (NSFC) [81970002, 81770003, 81270060, 81400396]; Shanghai Natural Science FoundationNatural Science Foundation of Shanghai [19ZR1408400]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT32019]
第一作者机构：[1]Eye Institute in Eye & ENT Hospital, and NHC Key Laboratory of Myopia, Fudan University, China[2]Shanghai Key Laboratory of Visual Impairment and Restoration, China[3]Key Laboratory of Myopia, Chinese Academy of Medical Sciences, China
通讯作者：
通讯机构：[4]Department of Physiology and Pathophysiology, Fudan University School of Basic Medical Sciences, China[6]Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China[*1]Department of Physiology and Pathophysiology, Fudan University School of Basic Medical Sciences. 130 Dong’an Rd., 207 seventh building, west campus, Shanghai 200032, China and Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
推荐引用方式(GB/T 7714)：
Zhou Xujiao,He Ding,Yan Xianxia,et al.Moxonidine inhibits excitatory inputs to airway vagal preganglionic neurons via activation of both alpha(2)-adrenoceptors and imidazoline I1 receptors[J].BRAIN RESEARCH.2020,1732:doi:10.1016/j.brainres.2020.146695.
APA：
Zhou, Xujiao,He, Ding,Yan, Xianxia,Chen, Xingxin,Li, Rui...&Wang, Jijiang.(2020).Moxonidine inhibits excitatory inputs to airway vagal preganglionic neurons via activation of both alpha(2)-adrenoceptors and imidazoline I1 receptors.BRAIN RESEARCH,1732,
MLA：
Zhou, Xujiao,et al."Moxonidine inhibits excitatory inputs to airway vagal preganglionic neurons via activation of both alpha(2)-adrenoceptors and imidazoline I1 receptors".BRAIN RESEARCH 1732.(2020)
