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Ethacrynic acid inhibits airway smooth muscle contraction in mice

ZHAO Xiao-Xue, CHEN Wei-Wei, CHEN Yuan-Yuan, LIU Meng-Su, LI Meng-Yue, CAO Lei, LIU Qing-Hua^*

Institute for Medical Biology & Hubei Province Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China; College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China

Abstract

The aim of this study was to investigate the inhibitory effect and the underlying mechanism of ethacrynic acid (EA) on the contraction in mice. BL-420S force measuring system was used to measure the tension of mouse tracheal rings. The whole cell patch clamp technique was utilized to record the channel currents of airway smooth muscle (ASM) cells. The calcium imaging system was used to determine the intracellular Ca2+ concentration ([Ca2+]i) in ASM cells. The results showed that EA significantly inhibited the high K+ (80 mmol/L) and acetylcholine (ACh, 100 µmol/L)-induced contraction of mouse tracheal rings in a dose-dependent manner. The maximal relaxation percentages were (97.02 ± 1.56)% and (85.21 ± 0.03)%, and the median effective concentrations were (40.28 ± 2.20) μmol/L and (56.22 ± 7.62) μmol/L, respectively. EA decreased the K+ and ACh-induced elevation of [Ca2+]i from 0.40 ± 0.04 to 0.16 ± 0.01 and from 0.50 ± 0.01 to 0.39 ± 0.01, respectively. In addition, EA inhibited L-type voltage-dependent calcium channel (LVDCC) and store-operated calcium channel (SOCC) currents in ASM cells, and Ca2+ influx. Moreover, EA decreased the resistance of the respiratory system (Rrs) in vivo in mice. These results indicated that EA inhibits LVDCC and SOCC, which results in termination of Ca2+ influx and decreases of [Ca2+]i, leading to relaxation of ASM. Taken together, EA might be a potential bronchodilator.

Key words: airway smooth muscle; L-type voltage-dependent calcium channel; store-operated calcium channel; ethacrynic acid

Received: 2019-03-19　　Accepted: 2019-07-10

Corresponding author: 刘庆华　　E-mail: liu258q@yahoo.com

DOI: 10.13294/j.aps.2019.0056

Citing This Article：

ZHAO Xiao-Xue, CHEN Wei-Wei, CHEN Yuan-Yuan, LIU Meng-Su, LI Meng-Yue, CAO Lei, LIU Qing-Hua. Ethacrynic acid inhibits airway smooth muscle contraction in mice. Acta Physiol Sin 2019; 71 (6): 863-873 (in Chinese with English abstract).