Cross-effect of TRPV1 and EP3 receptor on coughs and bronchopulmonary C-neural activities.
Cross-effect of TRPV1 and EP3 receptor on coughs and bronchopulmonary C-neural activities.
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DOI：
10.1371/journal.pone.0246375
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Gao X;Zhuang J;Zhao L;Wei W;Xu F
前列腺素E2 （PGE2）诱导的体内咳嗽和体外迷走神经去极化可被全身和局部给予前列腺素EP3受体（L-798106）和TRPV1拮抗剂（JNJ 17203212）抑制。这些结果表明，TRPV1可能通过迷走感觉神经调节EP3受体介导的PGE2咳嗽反应。本研究旨在确定1)吸入雾化JNJ 17203212和L-798106是否影响咳嗽对柠檬酸（CA，主要刺激TRPV1）和PGE2的反应；2) TRPV1和EP3受体在迷走肺c神经元（结节/颈神经节支气管肺c纤维细胞体）个体中形态共表达和电生理功能；3) TRPV1和EP3受体对这些神经兴奋存在交叉作用。为此，未麻醉的豚鼠在没有或以气溶胶形式给予每种拮抗剂的情况下吸入雾化的CA或PGE2。应用免疫荧光技术鉴定迷走肺c神经元中TRPV1和EP3受体的共表达（由DiI逆行追踪）。采用全细胞电压膜片钳法检测迷走肺c神经元中辣椒素（CAP）和pge2诱导的电流，并确定TRPV1和EP3受体拮抗剂对诱发电流的影响。我们发现JNJ 17203212或L-798106能减弱pge2诱导的咳嗽，而只有JNJ 17203212能显著抑制ca诱发的咳嗽。约1/4的迷走肺c神经元共表达EP3，细胞大小< 20 μm。CAP-和pge2诱导的电流在部分迷走肺c神经元个体中均有记录。前者仅被JNJ 17203212抑制，后者被JNJ 17203212或L-798106抑制。两种拮抗剂对咳嗽和迷走肺c -神经活性的交叉作用的相似性表明，共同表达TRPV1和EP3受体的迷走肺c -神经元亚群至少在一定程度上对PGE2的咳嗽反应负责。
Prostaglandin E2 (PGE2)-induced coughs in vivo and vagal nerve depolarization in vitro are inhibited by systemic and local administration of prostaglandin EP3 receptor (L-798106) and TRPV1 antagonists (JNJ 17203212). These results indicate a modulating effect of TRPV1 on the EP3 receptor-mediated cough responses to PGE2 likely through the vagal sensory nerve. This study aimed to determine whether 1) inhalation of aerosolized JNJ 17203212 and L-798106 affected cough responses to citric acid (CA, mainly stimulating TRPV1) and PGE2; 2) TRPV1 and EP3 receptor morphologically are co-expressed and electrophysiologically functioned in the individual of vagal pulmonary C-neurons (cell bodies of bronchopulmonary C-fibers in the nodose/jugular ganglia); and 3) there was a cross-effect of TRPV1 and EP3 receptor on these neural excitations. To this end, aerosolized CA or PGE2 was inhaled by unanesthetized guinea pigs pretreated without or with each antagonist given in aerosol form. Immunofluorescence was applied to identify the co-expression of TRPV1 and EP3 receptor in vagal pulmonary C-neurons (retrogradely traced by DiI). Whole-cell voltage patch clamp approach was used to detect capsaicin (CAP)- and PGE2-induced currents in individual vagal pulmonary C-neurons and determine the effects of the TRPV1 and EP3 receptor antagonists on the evoked currents. We found that PGE2-induced cough was attenuated by JNJ 17203212 or L-798106 and CA-evoked cough greatly suppressed only by JNJ 17203212. Approximately 1/4 of vagal pulmonary C-neurons co-expressed EP3 with a cell size < 20 μm. Both CAP- and PGE2-induced currents could be recorded in the individuals of some vagal pulmonary C-neurons. The former was largely inhibited only by JNJ 17203212, while the latter was suppressed by JNJ 17203212 or L-798106. The similarity of the cross-effect of both antagonists on cough and vagal pulmonary C-neural activity suggests that a subgroup of vagal pulmonary C-neurons co-expressing TRPV1 and EP3 receptor is, at least in part, responsible for the cough response to PGE2.
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DOI：
10.1152/ajpregu.00044.2010
发表时间：
2011-02-01
影响因子：
2.8
作者：
Canning, Brendan J.;Mori, Nanako
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发表时间：
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