Abstract.
In cystic fibrosis airway epithelia, mutation of the CFTR protein causes a reduced response of Cl− secretion to secretagogues acting via cAMP. Using a Ca2+ imaging system, the hypothesis that CFTR activation may permit ATP release and regulate [Ca2+] i via a receptor-mediated mechanism, is tested in this study. Application of external nucleotides produced a significant increase in [Ca2+] i in normal (16HBE14o− cell line and primary lung culture) and in cystic fibrosis (CFTE29o− cell line) human airway epithelia. The potency order of nucleotides on [Ca2+] i variation was UTP ≫ ATP > UDP > ADP > AMP > adenosine in both cell types. The nucleotide [Ca2+] i response could be mimicked by activation of CFTR with forskolin (20 μm) in a temperature-dependent manner. In 16HBE14o− cells, the forskolin-induced [Ca2+] i response increased with increasing temperature. In CFTE29o− cells, forskolin had no effect on [Ca2+] i at body temperature-forskolin-induced [Ca2+] i response in CF cells could only be observed at low experimental temperature (14°C) or when cells were cultured at 26°C instead of 37°C. Pretreatment with CFTR channel blockers glibenclamide (100 μm) and DPC (100 μm), with hexokinase (0.5 U/mg), and with the purinoceptor antagonist suramin (100 μm), inhibited the forskolin [Ca2+] i response. Together, these results demonstrate that once activated, CFTR regulates [Ca2+] i by mediating nucleotide release and activating cell surface purinoceptors in normal and CF human airway epithelia.
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Received: 3 April 2000/Revised: 30 June 2000
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Walsh, D., Harvey, B. & Urbach, V. CFTR Regulation of Intracellular Calcium in Normal and Cystic Fibrosis Human Airway Epithelia. J. Membrane Biol. 177, 209–219 (2000). https://doi.org/10.1007/s002320010004
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DOI: https://doi.org/10.1007/s002320010004