更新于：2024-11-01

chloride channel x Potassium channel

更新于：2024-11-01

基本信息

关联

项与 chloride channel x Potassium channel 相关的药物

Benzylhydrochlorothiazide

苄基氢氯噻嗪

靶点

Potassium channel x chloride channel

作用机制

钾离子通道调节剂 [+1]

在研机构

KYORIN Pharmaceutical Co., Ltd.

原研机构

KYORIN Pharmaceutical Co., Ltd.

在研适应症

心源性水肿 [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1961-01-31

100 项与 chloride channel x Potassium channel 相关的临床结果

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100 项与 chloride channel x Potassium channel 相关的转化医学

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0 项与 chloride channel x Potassium channel 相关的专利（医药）

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349

项与 chloride channel x Potassium channel 相关的文献（医药）

2024-11-01·Journal of Neuroscience Methods

Evaluation of cerebrospinal fluid (CSF) and interstitial fluid (ISF) mouse proteomes for the validation and description of Alzheimer’s disease biomarkers

Article

作者: Pahnke, Jens ; Brüning, Thomas ; Santos-García, Irene ; Eiriz, Ivan ; Górska, Anna Maria ; Nyman, Tuula

BACKGROUNDMass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain.NEW METHODWe performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice.RESULTSWe identified up to 625 proteins in ISF and 4483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated.COMPARISON WITH EXISTING METHODSThis newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone.CONCLUSIONSThe use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.

2024-10-01·American Journal of Physiology-Gastrointestinal and Liver Physiology

Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder

Article

作者: Holmes, Jenny ; Friedenberg, Steven G. ; Stauffer, Stephen H. ; Mathews, Kyle G. ; Meredith, Bryanna ; Vandewege, Michael W. ; Meurs, Kathryn ; Gookin, Jody L. ; Seiler, Gabriela S. ; Clarke, Lane L. ; Torres-Machado, Nicole

Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.

2024-08-15·Journal of Clinical Investigation

Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator correctors VX-445 and VX-121

Article

作者: Sembrat, John ; Wills, Zachary P ; Taiclet, Stefanie ; Straub, Adam C ; Kolski-Andreaco, Aaron ; Myerburg, Michael M ; Bridges, Robert J ; Devor, Daniel C ; Butterworth, Michael B

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, ultimately leading to diminished transepithelial anion secretion and mucociliary clearance. CFTR correctors are therapeutics that restore the folding/trafficking of mutated CFTR to the plasma membrane. The large-conductance calcium-activated potassium channel (BKCa, KCa1.1) is also critical for maintaining lung airway surface liquid (ASL) volume. Here, we show that the class 2 (C2) CFTR corrector VX-445 (elexacaftor) induces K+ secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BKCa antagonist paxilline. Similar results were observed with VX-121, a corrector under clinical evaluation. Whole-cell patch-clamp recordings verified that CFTR correctors potentiated BKCa activity from both primary HBEs and HEK cells stably expressing the α subunit (HEK-BK cells). Furthermore, excised patch-clamp recordings from HEK-BK cells verified direct action on the channel and demonstrated a significant increase in open probability. In mouse mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced firing frequency in primary rat hippocampal and cortical neurons. We raise the possibilities that C2 CFTR correctors gain additional clinical benefit by activation of BKCa in the lung yet may lead to adverse events through BKCa activation elsewhere.