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CFTR is activated through stimulation of purinergic P2Y2 receptors

  • Signaling and Cell Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

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 P2Y2 receptors in CFTR-expressing oocytes and in airway epithelial cells activates CFTR Cl− currents. Activation of CFTR Cl− currents via P2Y2 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 P2Y2 receptors was enhanced when Gi proteins were inhibited by pertussis toxin. Inhibition of protein kinase A and of protein kinases downstream of P2Y2 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 P2Y2 receptors: CFTR is inhibited by stimulation of Gi proteins and is activated by stimulation of Gq/11/PLC and an unknown downstream protein kinase.

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Acknowledgments

This study was supported by DFG SFB699 A6, DFG KU 756/8-2. We acknowledge the generous supply of Grk-2 cDNA by Prof. Dr. D. I. Cook, University of Sydney. We acknowledge the expert technical assistance by Ms. E. Tartler and Ms. A. Paech.

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Authors and Affiliations

  1. Department of Physiology, University of Regensburg, Regensburg, Germany

    Diana Faria, Rainer Schreiber & Karl Kunzelmann

  2. Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal

    Diana Faria

  3. Centre of Human Genetics, National Institute of Health, Lisboa, Portugal

    Diana Faria

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  1. Diana Faria
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  2. Rainer Schreiber
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  3. Karl Kunzelmann
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Correspondence to Karl Kunzelmann.

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Faria, D., Schreiber, R. & Kunzelmann, K. CFTR is activated through stimulation of purinergic P2Y2 receptors. Pflugers Arch - Eur J Physiol 457, 1373–1380 (2009). https://doi.org/10.1007/s00424-008-0606-2

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  • DOI: https://doi.org/10.1007/s00424-008-0606-2

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