title: Role of Ca2+ -activated ion transport in the treatment of cystic fibrosis.
abstract: Cystic fibrosis (CF) is caused by defective cyclic AMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Therefore, CF epithelial cells fail to transport, Cl(-) and water. Furthermore, the cessation of Cl(-) efflux across the apical membrane of CF pancreatic and biliary duct cells reduces HCO(3) (-) secretion as well. In CF epithelial cells activation of calcium-dependent Cl(-) channels might substitute for impaired CFTR function and restore Cl(-) and/or HCO(3) (-) secretion. ATP-mediated stimulation of P2Y and P2X purinergic receptors causes an increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)). Effects of ATP are influenced by external zinc, pH and Na(+) concentrations. In low Na(+), alkaline environment, ATP and zinc induce a sustained and reproducible Ca(2+) signal because of P2X receptor mediated Ca(2+) influx from the extracellular space. Importantly, the increase in [Ca(2+)](i) stimulates anion secretion of nasal epithelia in CF mouse models suggesting that targeting P2X receptors might have beneficial effects in CF therapy.
authors.affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary. zsembery@elet2.sote.hu
authors.forename: Akos
authors.initials: A
authors.lastname: Zsembery
authors.forename: Dóra
authors.initials: D
authors.lastname: Hargitai
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000503:physiopathology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology*; D027963:Chloride-Bicarbonate Antiporters / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D018181:Mice, Inbred CFTR; D010183:Pancreatic Ducts / Q000187:drug effects / Q000503:physiopathology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D053503:Epithelial Sodium Channels; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D015032:Zinc