Inhibition of the Na<sup>+</sup>/Ca<sup>2+</sup>Exchanger NCX<sub>1</sub>Expressed in <i>Xenopus</i>Oocyte by Glycyrrhizic Acid and Cyclophylin A

• 作者: Beibei Xing Jan Laudenbach Quanbao Gu Silvia Schwarz Wolfgang Schwarz Yinfang Xu Yu Wang
• 来源期刊: 生物科学与医学(英文)
• 学科: 医学
• 关键词: Sodium-Calcium EXCHANGER Asthma Voltage Clamp Glycyrrhizic Acid Cyclophylin A
• 年，卷（期）: swkxyyxyw_2017,（3）
• 页码范围: 128-141
• 页数: 14页
• 分类号: R73

摘要

The Na+/Ca2+ exchanger plays an important role in regulation of airway smooth muscle contraction by regulating intracellular calcium, and is a potential target for treatment of asthma. To test modulation of exchanger activity, we used Xenopus oocytes as model system. Na+/Ca2+ exchanger was expressed in the cells by microinjection of cRNA of the exchanger isoform NCX1. The activity of NCX1 was determined as Ni2+-sensitive current under voltage clamp in low Cl– medium and in the presence of the Cl–-channel inhibitor niflumic acid. Only this composition of solution allowed determining NCX1-mediated current with sufficient accuracy. Among a few tested Chinese herbal drugs, glycyrrhizic acid turned out to be a potent inhibitor of NCX1 with an apparent IC50 value of 40 μM. Previous work had revealed elevated cyclophylin A concentration in serum of asthmatic rats after receiving acupuncture treatment. Extracellular incubation of the oocytes in cyclophylin A for one day led to significant inhibition with an apparent IC50 value of about 1 μM. We suggest that effects of acupuncture and application of glycyrrhizic acid as an active constituent of Chinese medicine for treatment of asthma symptoms may partially be attributed to inhibition of the reversed mode of NCX1 and that these compounds may stimulate the search for new anti-asthmatic drugs.