CFTR Regulation of Intracellular Calcium in Normal and Cystic Fibrosis Human Airway Epithelia

CFTR Regulation of Intracellular Calcium in Normal and Cystic Fibrosis Human Airway Epithelia 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

CFTR Regulation of Intracellular Calcium in Normal and Cystic Fibrosis Human Airway Epithelia

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Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 2000 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s002320010004
Publisher site
See Article on Publisher Site

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.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Oct 1, 2000

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