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Int J Physiol Pathophysiol Pharmacol 2011;3(4):249-256.
An anti-coagulation agent Futhan preferentially targets GABAA receptors in lung
epithelia: implication in treating asthma
Xuanmao Chen, Minghua Li, Zhi-Gang Xiong, Beverley A. Orser, John F. MacDonald, Wei-Yang Lu
Department of Physiology, University of Toronto, Canada; Department of Anesthesia, University of Toronto, Canada; Sunnybrook Health
Sciences Centre, University of Toronto, Canada; Robarts Research Institute, University of Western Ontario, Canada; Robert S. Dow
Neurobiology Laboratories, Legacy Research, Portland, USA; Department of Neurobiology, Morehouse School of Medicine, Atlanta,
Received August 10, 2011; accepted October 19, 2011; Epub November 15, 2011; Published December 15, 2011
Abstract: 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 GABAA receptors both in hippocampal neurons and in A549 cells, a human alveolar epithelial cell line. The effect of
Futhan on GABAA receptors in A549 cells is much more potent than its effect on GABAA receptors in hippocampal neurons (IC50: 0.9
µM v.s. 7.3 µM). Since GABAA 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 GABAA receptors in the lung. (IJPPP1108002).
Keywords: Asthma, GABAA receptors, NMDA receptors, Futhan, ion channels
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Address all correspondence to:
Dr. John F. MacDonald
Molecular Brain Research Group
Robarts Research Institute
University of Western Ontario
100 Perth Drive, London, ON, Canada N6A 5K8.