Activation of Adenosine Triphosphate-Gated Purinergic 2 Receptor Channels by Transient Receptor Potential Vanilloid Subtype 4 in Cough Hypersensitivity

瞬时受体电位通道 嘌呤能受体 嘌呤能信号 化学 三磷酸腺苷 药理学 腺苷受体 腺苷 受体 医学 神经科学 生物化学 生物 兴奋剂
作者
Wanzhen Li,Shengyuan Wang,Tongyangzi Zhang,Yiqing Zhu,Li Yu,Xianghuai Xu
出处
期刊:Biomolecules [Multidisciplinary Digital Publishing Institute]
卷期号:15 (2): 285-285
标识
DOI:10.3390/biom15020285
摘要

Background: Transient receptor potential vanilloid subtype 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that is involved in the development of cough hypersensitivity. Purinergic 2 receptors (P2X) belong to a class of adenosine triphosphate (ATP)-gated non-selective cation channels that also play an important role in cough hypersensitivity. Nevertheless, little is known about the interaction between them for cough hypersensitivity. The present study was designed to clarify the roles of TRPV4 and ATP-P2X receptors in cough hypersensitivity, and to explore the possible involvement of ATP-P2X receptors in the development of cough hypersensitivity mediated by TRPV4. Design and Method: This study aims to establish a guinea pig model of citric acid-induced enhanced cough to confirm the effects of the TRPV4-mediated purinergic signaling pathway on cough sensitivity by testing the number of coughs, the release of ATP, and the expressions of P2X and TRPV4 receptors in the tracheal carina and vagal ganglion; recording the activity of cellular currents with the whole-cell patch clamp technique; and detecting changes in intracellular calcium flow in the vagus nerve cells. Results: The number of coughs in the TRPV4 agonist GSK1016790A-treated control group was elevated compared with that in the control group, whereas the number of coughs in the TRPV4 antagonist HC067047-treated model group was significantly reduced compared with that in the chronic cough group. When the individuals in the chronic cough group were treated with A317491, PSB12062, and A804598 (P2X3,4,7 antagonists), the number of coughs was significantly decreased. This suggests that TRPV4 and P2X3, P2X4, and P2X7 receptors have an effect on cough hyper-responsiveness in guinea pigs with chronic cough. Enzyme-linked immunosorbent assay results suggested that TRPV4 antagonist and P2X3,4,7 antagonist could differentially reduce the levels of inflammatory factor SP and CGRP in alveolar lavage fluid, and TRPV4 antagonist could reduce the ATP content in the alveolar lavage fluid of guinea pigs in the model. Western blot and immunohistochemistry results showed that, in the tracheal carina and vagal ganglion, the TRPV4 and P2X3,4,7 expression was elevated in the chronic cough group compared with the control group, and could be significantly inhibited by TRPV4 antagonist. Vagus ganglion neurons were isolated, cultured, identified, and subjected to whole-cell membrane clamp assay. When ATP was given extracellularly, a significant inward current was recorded in the examined cells of individuals in the chronic cough and control groups, and the inward current induced by ATP was higher in the chronic cough group relative to the control group. This inward current (IATP) was differentially blocked by P2X3, P2X4, and P2X7 antagonists. Further studies revealed that TRPV4 agonists potentiated ATP-activated currents, and the potentiated currents could still be inhibited by P2X3, P2X4, and P2X7 receptor antagonists, whereas TRPV4 inhibitors partially blocked ATP-activated currents. It is suggested that TRPV4 affects P2X3, P2X4, and P2X7 receptor-mediated ATP-activated currents. Calcium imaging also showed that TRPV4 agonists induced different degrees of calcium inward currents in the vagal neurons of the chronic cough and the control group, and the calcium inward currents were more significant in the model group. Conclusions: The TRPV4-mediated purinergic signaling pathway was identified to be involved in the development of cough hypersensitivity in guinea pigs with chronic cough; i.e., TRPV4 can lead to the release of airway epithelial ATP, which can stimulate P2X receptors on the cough receptor, and further activate the sensory afferent nerves in the peripheral airway, leading to increased cough sensitivity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
1秒前
李健应助naomi采纳,获得10
2秒前
Andy1201完成签到,获得积分10
2秒前
林小不脏完成签到,获得积分10
2秒前
enen发布了新的文献求助30
2秒前
greenspanee发布了新的文献求助10
2秒前
2秒前
2秒前
Loone发布了新的文献求助10
4秒前
Akim应助lunar采纳,获得10
4秒前
元谷雪发布了新的文献求助10
5秒前
刘敏123456完成签到,获得积分20
5秒前
油菜的星星完成签到,获得积分10
5秒前
马某某某某某完成签到,获得积分10
5秒前
5秒前
雪糕刺客发布了新的文献求助10
5秒前
6秒前
6秒前
建设发布了新的文献求助10
6秒前
Xiaojiu发布了新的文献求助10
7秒前
DGFR发布了新的文献求助10
7秒前
JPH1990发布了新的文献求助10
8秒前
8秒前
8秒前
8秒前
不安太阳完成签到,获得积分10
8秒前
9秒前
张舒涵发布了新的文献求助10
10秒前
10秒前
guojin发布了新的文献求助10
11秒前
刘敏123456发布了新的文献求助20
11秒前
久久发布了新的文献求助10
11秒前
云清发布了新的文献求助10
12秒前
秋秋大王发布了新的文献求助10
12秒前
建设完成签到,获得积分10
13秒前
clairr完成签到,获得积分10
13秒前
enen完成签到,获得积分20
13秒前
啊伟发布了新的文献求助30
13秒前
在水一方应助zjh采纳,获得10
13秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Effective Learning and Mental Wellbeing 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3974426
求助须知:如何正确求助?哪些是违规求助? 3518788
关于积分的说明 11195842
捐赠科研通 3254946
什么是DOI,文献DOI怎么找? 1797649
邀请新用户注册赠送积分活动 877037
科研通“疑难数据库(出版商)”最低求助积分说明 806130