Intralaryngeal application of ATP evokes apneic response mainly via acting on P2X3 (P2X2/3) receptors of the superior laryngeal nerve in postnatal rats.

Intralaryngeal application of ATP evokes apneic response mainly via acting on P2X3 (P2X2/3) receptors of the superior laryngeal nerve in postnatal rats.
复制标题

喉内应用 ATP 主要通过作用于出生后大鼠喉上神经的 P2X3 (P2X2/3) 受体引起呼吸暂停反应。

DOI:
10.1152/japplphysiol.00091.2021
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发表时间:
2021
期刊:
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子:
--
通讯作者:
Xu,Fadi
Xu,Fadi
中科院分区:
--
文献类型:
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作者:
Zhuang,Jianguo;Gao,Xiuping;Wei,Wan;Pelleg,Amir;Xu,Fadi

文献摘要

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雾化的5 ' -三磷酸腺苷(ATP)通过激活迷走神经感觉纤维P2X3和P2X2/3受体(P2X3R和P2X2/3R)诱导咳嗽和支气管收缩。本研究的目的是确定这些受体对喉上神经(SLN)介导的心肺对ATP刺激反应的影响。我们比较了a -317491(一种P2X3R和P2X2/3R拮抗剂)喉内灌注前后大鼠幼崽对ATP或α,β-亚甲基ATP的心肺反应;2) SLN的双边段;3) sln周围用辣椒素治疗(阻断喉上c纤维(slcf)的传导)或A-317491。测定P2X3R和P2X2R在结/颈节喉感觉神经元中的免疫反应性(IR)。最后,采用全细胞膜片钳记录测定未处理和处理a -317491的ATP-或α,β-亚甲基ATP (α,β-mATP)诱导电流。结果发现,咽内灌注ATP和α,β-mATP均可引起立即呼吸暂停,高血压和心动过缓。通过喉内灌注A-317491和用A-317491或辣椒素进行SLN周围治疗,呼吸暂停被消除,高血压和心动过缓被钝化,尽管所有的心肺反应都通过SLN的双侧切面被消除。用荧光金(FG)标记结节和颈静脉神经节神经元,观察到P2X3R-和P2X2R-IR。应用A-317491后,喉部c神经元ATP-和α,β- map -诱导电流分别减少75%和95%。综上所述,麻醉大鼠幼鼠对咽内灌注ATP或α,β-mATP的心肺反应主要是由SLCFs的P2X3R-P2X2/3R激活介导的。溶化ATP通过激活位于迷走肺感觉纤维上的P2X3和P2X2/3受体(P2X3R和P2X2/3R)诱导咳嗽和支气管收缩。喉上神经(SLN),特别是SLN c -纤维(slcf),与呼吸暂停、高血压和心动过缓有关。本研究首次证明,ATP或α,β-mATP作用于喉粘膜,主要通过激活slcf上的P2X3R-P2X2/3R引起这些心肺反应。
Aerosolized adenosine 5′-triphosphate (ATP) induces cough and bronchoconstriction by activating vagal sensory fibers’ P2X3 and P2X2/3 receptors (P2X3R and P2X2/3R). The goal of this study is to determine the effect of these receptors on the superior laryngeal nerve (SLN)-mediated cardiorespiratory responses to ATP challenge. We compared the cardiorespiratory responses to intralaryngeal perfusion of either ATP or α,β-methylene ATP in rat pups before and after1) intralaryngeal perfusion of A-317491 (a P2X3R and P2X2/3R antagonist);2) bilateral section of the SLN; and3) peri-SLN treatment with capsaicin (to block conduction in superior laryngeal C-fibers, SLCFs) or A-317491. The immunoreactivity (IR) of P2X3R and P2X2R was determined in laryngeal sensory neurons of the nodose/jugular ganglia. Lastly, a whole cell patch clamp recording was used to determine ATP- or α,β-methylene ATP (α,β-mATP)-induced currents without and with A-317491 treatment. It was found that intralaryngeal perfusion of both ATP and α,β-mATP induced immediate apnea, hypertension, and bradycardia. The apnea was eliminated and the hypertension and bradycardia were blunted by intralaryngeal perfusion of A-317491 and peri-SLN treatment with either A-317491 or capsaicin, although all of the cardiorespiratory responses were abolished by bilateral section of the SLN. P2X3R- and P2X2R-IR were observed in nodose and jugular ganglionic neurons labeled by fluoro-gold (FG). ATP- and α,β-mATP-induced currents recorded in laryngeal C-neurons were reduced by 75% and 95%, respectively, by the application of A-317491. It is concluded that in anesthetized rat pups, the cardiorespiratory responses to intralaryngeal perfusion of either ATP or α,β-mATP are largely mediated by the activation of SLCFs’ P2X3R-P2X2/3R.NEW & NOTEWORTHYAerosolized ATP induces cough and bronchoconstriction via activating P2X3 and P2X2/3 receptors (P2X3R and P2X2/3R) localized on vagal pulmonary sensory fibers. The superior laryngeal nerve (SLN), particularly SLN C-fibers (SLCFs), is involved in generating apnea, hypertension, and bradycardia. This study demonstrates for the first time that either ATP or α,β-mATP applied onto the laryngeal mucosa elicit these cardiorespiratory responses predominately through the activation of P2X3R-P2X2/3R localized on SLCFs.