Asthmatic Augmentation of Airway Vagal Activity Involves Decreased Central Expression and Activity of CD73 in Rats

作者：Chen, Xingxin; Zeng, Ming; He, Ding; Yan, Xianxia; Chen, Hong; Chen, Yonghua; Xia, Chunmei; Wang, Jin; Shen, Linlin; Zhu, Danian; Wang, Jijiang

来源：ACS Chemical Neuroscience, 2019, 10(6): 2809-2822.

DOI：10.1021/acschemneuro.9b00023

• ecto-5 '-nucleotidase
• asthma
• vagus nerve
• airway
• patch-clamp
• neuron

The severity of asthma is closely related to the intensity of airway vagal activity; however, it is unclear how airway vagal activity is centrally augmented in asthma. Here we report that in an asthma model of male Sprague-Dawley rats, the expression and activity of ecto-5'-nucleotidase (CD73) were decreased in airway vagal centers, ATP concentration in cerebral spinal fluid was increased, and the inhibitory and excitatory airway vagal responses to intracisternally injected ATP (5 mu mol) and CD73 inhibitor AMPCP (5 mu mol), respectively, were attenuated. In airway vagal preganglionic neurons (AVPNs) identified in medullary slices of neonatal Sprague-Dawley rats, AMPCP (100 mu mol.L-1) caused excitatory effects, as are shown in patch-clamp by depolarization, increased neuronal discharge, and facilitated spontaneous excitatory postsynaptic currents (sEPSCs). In contrast, exogenous ATP (100 mu mol.L-1, 1 mmol.L-1) primarily caused inhibitory effects, which are similar to those induced by exogenous adenosine (100 mu mol.L-1). Adenosine A(1) receptor antagonist CPT (5 mu mol.L-1) blocked the inhibition of sEPSCs induced by 100 mu mol.L-1 exogenous ATP and that by 100 mu mol.L-1 exogenous adenosine, whereas 50 mu mol.L-1 CPT converted the inhibition of sEPSCs induced by 1 mmol.L-1 ATP to facilitation that was blocked by addition of P2X receptor antagonist PPADS (20 mu mol.L-1). These results demonstrate that in rat, the sEPSCs of AVPNs are facilitated by extracellular ATP via activation of P2X receptors and inhibited by extracellular adenosine via activation of A(1) receptors; in experimental asthma, decreased CD73 expression and activity in airway vagal centers contribute to the augmentation of airway vagal activity through imbalanced ATP/ADO modulation of AVPNs.

• 出版日期2019-6
• 单位复旦大学