An anti-coagulation agent Futhan preferentially targets GABAA receptors in lungepithelia: implication in treating asthma

International Journal of Physiology, Pathophysiology and Pharmacology

Wei-Yang Lu¹  Xuanmao Chen¹  Beverley A Orser¹  Zhi-Gang Xiong¹  Minghua Li¹  John F MacDonald¹ 

关键词: Asthma;    GABAA receptors;    NMDA receptors;    Futhan;    ion channels;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Futhan is a serine protease inhibitor and medicine in the treatment of disseminated intravascular coagulation (DIC) and acute pancreatitis. It is metabolized quickly in vivo. Here we show that Futhan reversibly inhibits NMDA receptors in hippocampal neurons and GABA_A receptors both in hippocampal neurons and in A549 cells, a human alveolar epithelial cell line. The effect of Futhan on GABA_A receptors in A549 cells is much more potent than its effect on GABA_A receptors in hippocampal neurons (IC₅₀: 0.9 μM V.S. 7.3 μM). Since GABA_A receptors are also expressed in various non-neuronal tissues, particularly in airway epithelia and GABA promotes mucus production during asthma, our findings indicate that Futhan may be developed as a novel aerosolized therapeutic to treat asthma through blocking GABA_A receptors in the lung.

【 授权许可】

Unknown