Acid-induced modulation of airway basal tone and contractility: Role of acid-sensing ion channels (ASICs) and TRPV1 receptor
Acid-induced modulation of airway basal tone and contractility: Role of acid-sensing ion channels (ASICs) and TRPV1 receptor
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DOI：
10.1016/j.lfs.2007.08.026
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发表时间：
2007-09-08
期刊：
影响因子：
6.1
通讯作者：
Devillier, Philippe
中科院分区：
文献类型：
--
作者：
Faisy, Chnistophe;Planquette, Benjamin;Devillier, Philippe
细胞外酸中毒在炎症性呼吸道疾病中的作用尚不清楚。组织酸化的一个后果是通过多模式W门控跨膜通道ASICs和TRPV1受体刺激感觉神经。本研究探讨了酸中毒对豚鼠气道基础张力和反应性的影响。酸中毒(pH 6.8，10分钟，37℃)显著降低气管环的基础张力(p<；0.01与配对对照相比)。此外，pH降低增加了气管环对乙酰胆碱的最大收缩(p<；0.05与配对对照相比)。ASIC1a或ASIC3/ASIC2a抑制剂(0.5 mM布洛芬，0.1 mM Gd)、一氧化氮合酶抑制剂(1 mM L-NAME)和鸟苷环化酶抑制剂(1 MU MODQ)可抑制pH诱导的气道基础张力松弛。相反，去除上皮或用TRPV1拮抗剂(1mU卡萨西平)、NK1.2.3受体拮抗剂(各0.1mU)、电压敏感性钠通道阻滞剂(1mU河豚毒素)、对ASICs无作用的环氧合酶抑制剂(1mU吲哚美辛)或ASIC3和ASIC3/ASIC2b抑制剂(10 nM双氯芬酸，i PM阿司匹林)预处理，均不能改变pH诱导的气道基础张力松弛。此外，去上皮、卡萨西平、NK1.2.3受体拮抗剂可抑制酸诱导的乙酰胆碱高反应性。河豚毒素、阿米洛利、布洛芬和双氯芬酸。综上所述，pH诱导的最初的气道松弛似乎不依赖于感觉神经，提示由平滑肌ASICs介导的对气道基础张力的调节。相反，pH诱导的高反应涉及感觉神经依赖的ASICs和TRPV1，以及一种未知的上皮组分对酸中毒的反应。(C)2007 Elsevier Inc.保留所有权利。
The role of extracellular acidosis in inflammatory airway diseases is not well known. One consequence of tissue acidification is the stimulation of sensory nerves via the polymodal W-gated transmembrane channels ASICs and TRPV1 receptor. The present study investigated the effect of acidosis on airway basal tone and responsiveness in the guinea pig. Acidosis (pH 6.8, 10 min, 37 degrees C) significantly decreased the basal tone of tracheal rings (p < 0.01 vs. paired control). Moreover, pH fall raised the maximal contraction of tracheal rings to acetylcholine (p < 0.05 vs. paired control). The pH-induced relaxation of airway basal tone was inhibited by pretreatments with ASIC1a or ASIC3/ASIC2a inhibitors (0.5 MM ibuprofen, 0.1 mM gadolinium), nitric oxide synthase inhibitor (1 mM L-NAME), and guanylate cyclase inhibitor (1 mu M ODQ). In contrast, the pH-induced relaxation of airway basal tone was not modified by epithelium removal or pretreatments with a TRPV1 antagonist (1 mu M capsazepine), a combination of NK1.2.3 receptor antagonists (0.1 mu M each), a blocker of voltage-sensitive Na+ channels (1 mu M tetrodotoxin), a cyclooxygenase inhibitor with no activity on ASICs (1 mu M indomethacin) or ASIC3 and ASIC3/ASIC2b inhibitors (10 nM diclofenac, I PM aspirin). Furthermore, acid-induced hyperresponsiveness to acetylcholine was inhibited by epithelium removal, capsazepine, NK1.2.3 receptor antagonists. tetrodotoxin, amiloride, ibuprofen and diclofenac. In summary, the initial pH-induced airway relaxation seems to be independent of sensory nerves, suggesting a regulation of airway basal tone mediated by smooth muscle ASICs. Conversely, the pH-induced hyperresponsiveness involves sensory nerves-dependent ASICs and TRPV1, and an unknown epithelial component in response to acidosis. (C) 2007 Elsevier Inc. All rights reserved.