Expression and function of CFTR in rat intrapulmonary arteries

¹ Institut de Physiologie et Biologie Cellulaires CNRS UMR 6187, Université de Poitiers, 40 Avenue du Recteur Pineau 86022 Poitiers, France
² INSERM U 885, Laboratoire de Physiologie Cellulaire Respiratoire, 146, rue Léo Saignat, F33076 Bordeaux; Université Bordeaux2, F33076 Bordeaux, France

^* To whom correspondence should be addressed. E-mail: christelle.guibert{at}u-bordeaux2.fr.

	Abstract

The CFTR gene encodes a cAMP-dependent chloride channel mainly located at the apical membrane of epithelial cells. In myocytes of pulmonary arteries, numerous chloride channels have been identified and described except CFTR. We thus investigated the presence and the function of CFTR in rat intrapulmonary arteries.

CFTR expression, localisation and function were analysed in cultured smooth muscle cells with RT-PCR and immunoprecipitation followed by PKA phosphorylation, immunolocalisation and iodide efflux assay respectively. The role of CFTR in pulmonary vasoreactivity was determined in arterial rings with an organ bath system.

RT-PCR and immunoprecipitation analyses as well as immunolocalisation study revealed the expression of CFTR transcripts and proteins. Iodide efflux assay shows the existence of functional cAMP-, calcium-, and volume-dependent chloride channels. Furthermore we found (i) inhibition of the forskolin/genistein-activated iodide efflux by glibenclamide, diphenylamine-2-carboxylic acid and the CFTR-specific inhibitor CFTR_inh-172 (ii) activation of iodide efflux by the CFTR activators benzoquinolizinium derivatives, MPB-07 and MPB-91 (iii) inhibition of MPB-dependent efflux by CFTR_inh-172. Finally, CFTR activators induced a concentration-dependent vasorelaxation in rings preconstricted with phenylephrine, in the presence of endothelium or not.

These results are the first to reveal functional cAMP-regulated CFTR contributing to endothelium-independent vasorelaxation in rat intrapulmonary arterial myocytes.

This article has been cited by other articles:

				J. Noe, D. Petrusca, N. Rush, P. Deng, M. VanDemark, E. Berdyshev, Y. Gu, P. Smith, K. Schweitzer, J. Pilewsky, et al. CFTR Regulation of Intracellular pH and Ceramides Is Required for Lung Endothelial Cell Apoptosis Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 314 - 323. [Abstract] [Full Text] [PDF]

				D. Hubert, F. Aubourg, B. Fauroux, L. Trinquart, I. Sermet, G. Lenoir, A. Clement, A. T. Dinh-Xuan, B. Louis, B. Mahut, et al. Exhaled nitric oxide in cystic fibrosis: relationships with airway and lung vascular impairments Eur. Respir. J., July 1, 2009; 34(1): 117 - 124. [Abstract] [Full Text] [PDF]