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 HCO3 - secretion as well. In CF epithelial cells activation of calcium-dependent Cl- channels might substitute for impaired CFTR function and restore Cl- and/or HCO3 - secretion. ATP-mediated stimulation of P2Y and P2X purinergic receptors causes an increase in cytosolic Ca2+ concentration ([Ca2+]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 Ca2+ signal because of P2X receptor mediated Ca 2+ influx from the extracellular space. Importantly, the increase in [Ca2+]i stimulates anion secretion of nasal epithelia in CF mouse models suggesting that targeting P2X receptors might have beneficial effects in CF therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 562-564 |
| Number of pages | 3 |
| Journal | Wiener Medizinische Wochenschrift |
| Volume | 158 |
| Issue number | 19-20 |
| DOIs | |
| Publication status | Published - Oct 2008 |
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Keywords
- Bicarbonate
- CFTR
- Intracellular pH
- Purinergic signaling
- Zinc
ASJC Scopus subject areas
- Medicine(all)
Cite this
Role of Ca2+-activated ion transport in the treatment of cystic fibrosis. / Zsembery, A.; Hargitai, Dóra.
In: Wiener Medizinische Wochenschrift, Vol. 158, No. 19-20, 10.2008, p. 562-564.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of Ca2+-activated ion transport in the treatment of cystic fibrosis
AU - Zsembery, A.
AU - Hargitai, Dóra
PY - 2008/10
Y1 - 2008/10
N2 - 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 HCO3 - secretion as well. In CF epithelial cells activation of calcium-dependent Cl- channels might substitute for impaired CFTR function and restore Cl- and/or HCO3 - secretion. ATP-mediated stimulation of P2Y and P2X purinergic receptors causes an increase in cytosolic Ca2+ concentration ([Ca2+]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 Ca2+ signal because of P2X receptor mediated Ca 2+ influx from the extracellular space. Importantly, the increase in [Ca2+]i stimulates anion secretion of nasal epithelia in CF mouse models suggesting that targeting P2X receptors might have beneficial effects in CF therapy.
AB - 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 HCO3 - secretion as well. In CF epithelial cells activation of calcium-dependent Cl- channels might substitute for impaired CFTR function and restore Cl- and/or HCO3 - secretion. ATP-mediated stimulation of P2Y and P2X purinergic receptors causes an increase in cytosolic Ca2+ concentration ([Ca2+]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 Ca2+ signal because of P2X receptor mediated Ca 2+ influx from the extracellular space. Importantly, the increase in [Ca2+]i stimulates anion secretion of nasal epithelia in CF mouse models suggesting that targeting P2X receptors might have beneficial effects in CF therapy.
KW - Bicarbonate
KW - CFTR
KW - Intracellular pH
KW - Purinergic signaling
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=55949135571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55949135571&partnerID=8YFLogxK
U2 - 10.1007/s10354-008-0596-x
DO - 10.1007/s10354-008-0596-x
M3 - Article
C2 - 18998073
AN - SCOPUS:55949135571
VL - 158
SP - 562
EP - 564
JO - Wiener Medizinische Wochenschrift
JF - Wiener Medizinische Wochenschrift
SN - 0043-5341
IS - 19-20
ER -