Faria, Diana and Schreiber, Rainer and Kunzelmann, Karl (2009) CFTR is activated through stimulation of purinergic P2Y(2) receptors. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 457 (6). pp. 1373-1380. ISSN 0031-6768,
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It has been reported that the cystic fibrosis transmembrane conductance regulator (CFTR) can be activated through cAMP- and protein kinase A-independent pathways involving GTP-binding proteins and an unknown kinase. In this study, we further examined how G protein-coupled pathways regulate CFTR. We demonstrate that stimulation of purinergic P2Y(2) receptors in CFTR-expressing oocytes and in airway epithelial cells activates CFTR Cl- currents. Activation of CFTR Cl- currents via P2Y(2) was inhibited by CFTRinh-172 and was independent of intracellular Ca2+, protein kinase C, or calmodulin-dependent kinase (CAMK). However, activation of CFTR was suppressed by inhibition of phospholipase C and by the nonselective protein kinase inhibitor staurosporine. Activation of CFTR through P2Y(2) receptors was enhanced when G(i) proteins were inhibited by pertussis toxin. Inhibition of protein kinase A and of protein kinases downstream of P2Y(2) receptors such as mitogen-activated protein kinases, tyrosine kinase, or c-src kinase did not interfere with activation of CFTR. The present results demonstrate an antagonistic regulation of CFTR by P2Y(2) receptors: CFTR is inhibited by stimulation of G(i) proteins and is activated by stimulation of G(q/11)/PLC and an unknown downstream protein kinase.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; AIRWAY EPITHELIAL-CELLS; RECTIFYING CHLORIDE CHANNELS; HETEROTRIMERIC G-PROTEINS; APICAL MEMBRANE; MOUSE TRACHEA; GROWTH-FACTOR; CL-CHANNELS; SWEAT-DUCT; KINASE; Cystic fibrosis transmembrane conductance regulator; CFTR; P2Y(2); GTP-binding proteins; G protein; G(i); G(q); Purinergic receptor; Ca2+-dependent Cl- secretion; CaCC |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2020 04:57 |
| Last Modified: | 21 Sep 2020 04:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29226 |
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