Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction

Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction
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DOI:
10.1016/j.pupt.2008.07.001
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发表时间:
2008-10-01
影响因子:
3.2
通讯作者:
Hasegawa, Yoshinori
Hasegawa, Yoshinori
中科院分区:
医学3区
文献类型:
--
作者:
Ito, Satoru;Kume, Hiroaki;Hasegawa, Yoshinori

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被称为冷受体激动剂的薄荷脑已被广泛用于缓解呼吸道症状,如咳嗽和胸部充血。先前的研究表明,薄荷醇可降低支气管收缩和气道高反应性。本研究的目的是检查薄荷醇和另一种冷受体激动剂icilin对气道平滑肌收缩的影响。使用从豚鼠分离的剥脱上皮的气管平滑肌组织监测等长力。细胞内Ca(2+)浓度通过Fura-2荧光测定。(-)甲氨蝶呤(0.01-1 mM)以浓度依赖性方式抑制乙酰甲胆碱(MCh,0.01-10 μ M)和高细胞外K(+)浓度(20-60 mM)诱导的收缩。此外,(-)薄荷醇还能显著抑制MCh或高K(+)引起的细胞内Ca(2+)浓度升高。Icilin(100 μ M)也能明显减弱MCh或高K(+)引起的收缩。1 mM(-)薄荷醇对MCH诱导收缩的抑制作用在低温(24-26 ℃)下显著高于37 ℃。本研究结果表明,抑制Ca(2+)内流在薄荷醇介导的抑制气道平滑肌收缩中起重要作用。此外,我们的研究结果表明,刺激未知的冷受体可能参与这些机制。这些发现表明,薄荷醇的使用有利于减轻呼吸道症状,因为它对气道平滑肌收缩具有抑制作用。(c)2008爱思唯尔有限公司保留所有权利。
Menthol, known as a cold receptor agonist, has widely been used in the relief of respiratory symptoms such as coughing and chest congestion. Previous studies have demonstrated that menthol reduces bronchoconstriction and airway hyperresponsiveness. The aim of this study was to examine the effects of menthol and icilin, another cold receptor agonist, on airway smooth muscle contraction. Isometric force was monitored using epithelium-denuded tracheal smooth muscle tissues isolated from guinea pigs. Intracellular Ca(2+) concentrations were assessed by fura-2 fluorescence. (-)Menthol (0.01-1 mM) inhibited contraction induced by methacholine (MCh, 0.01-10 mu M) and high extracellular K(+) concentrations (20-60 mM) in a concentration-dependent manner. Moreover, the increases of intracellular Ca(2+) concentrations induced by MCh or high K(+) were significantly reduced by (-)menthol. Icilin (100 mu M) also significantly attenuated contraction induced by MCh or high K(+). The inhibitory effect of 1 mM (-)menthol on MCh-induced contraction was significantly higher at cool temperature (24-26 degrees C) than at 37 degrees C. The present results demonstrate that inhibition of Ca(2+) influx plays an important role in the menthol-mediated inhibition of contraction in airway smooth muscle. Furthermore, our findings indicate that stimulation of unknown cold receptors may be involved in these mechanisms. These findings suggest that the use of menthol is beneficial for reducing respiratory symptoms because of its inhibitory effects on airway smooth muscle contraction. (c) 2008 Elsevier Ltd. All rights reserved.