Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A)
نویسندگان
چکیده
منابع مشابه
Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways.
For almost two decades, it has been postulated that calcium-activated Cl(-) channels (CaCCs) play a role in airway epithelial Cl(-) secretion, but until recently, the molecular identity of the airway CaCC(s) was unknown. Recent studies have unequivocally identified TMEM16A as a glandular epithelial CaCC. We have studied the airway bioelectrics of neonatal mice homozygous for a null allele of Tm...
متن کاملAntagonists of the TMEM16A calcium-activated chloride channel modulate airway smooth muscle tone and intracellular calcium.
BACKGROUND Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. METHODS Human ASM, guinea pig tracheal rings, o...
متن کاملCalcium-calmodulin does not alter the anion permeability of the mouse TMEM16A calcium-activated chloride channel
The transmembrane protein TMEM16A forms a Ca(2+)-activated Cl(-) channel that is permeable to many anions, including SCN(-), I(-), Br(-), Cl(-), and HCO3 (-), and has been implicated in various physiological functions. Indeed, controlling anion permeation through the TMEM16A channel pore may be critical in regulating the pH of exocrine fluids such as the pancreatic juice. The anion permeability...
متن کاملExpression Cloning of TMEM16A as a Calcium-Activated Chloride Channel Subunit
Calcium-activated chloride channels (CaCCs) are major regulators of sensory transduction, epithelial secretion, and smooth muscle contraction. Other crucial roles of CaCCs include action potential generation in Characean algae and prevention of polyspermia in frog egg membrane. None of the known molecular candidates share properties characteristic of most CaCCs in native cells. Using Axolotl oo...
متن کاملA comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity
TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sens...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2017
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.7b00020