Published ahead of print on March 6, 2003, doi:10.1165/rcmb.2002-0104OC
© 2003 American Thoracic Society DOI: 10.1165/rcmb.2002-0104OC Effects of Endothelin-1 on Epithelial Ion Transport in Human AirwaysLaboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, Boulogne; INSERM U339 UFR Saint Antoine, Paris; Département de Biophysique, University of Lille, Lille; Institut de Pharmacologie, Paris, France; and Département de Physiologie, University of Lille, Lille, France Address correspondence to: Professeur Thierry Chinet, Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, UFR Paris Ile de France Ouest, Université de Versailles Saint Quentin en Yvelines, Hôpital Ambroise Paré, 9 avenue Charles de Gaulle, 92104 Boulogne cedex, France. E-mail: thierry.chinet{at}apr.ap-hop-paris.fr Endothelin-1 (ET-1) exerts many biological effects in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation. We investigated the effect of ET-1 on Na absorption and Cl secretion in human bronchial epithelial cells. Addition of 10-7 M ET-1 had no effect on the inhibition of the short circuit current (Isc) induced by amiloride, a Na channel blocker. Addition of 10-7 M ET-1 to the apical bath in the presence of amiloride increased Isc in cultured human bronchial epithelial cells studied in Ussing chambers. No effect was observed when ET-1 was added to basolateral bath, indicating that the involved ET-1 receptors are likely present only in the apical membrane of the cells. Use of Cl-free solutions and bumetanide reduced the ET-1–induced increases in Isc, indicating that ET-1 stimulates Cl secretion. The ET-1–induced increase in Isc was prevented by exposure to the ETB receptor antagonist BQ-788 but not to the ETA receptor antagonist BQ-123. ET-1 did not raise intracellular Ca levels, but increased the intracellular concentration of cAMP. These findings indicate that ET-1 is a Cl secretagogue in human airways and acts presumably through apically located ETB receptors and activation of the cAMP pathway.
Abbreviations: intracellular free Ca concentration, [Ca]i • cyclic adenosine monophosphate, cAMP • Dulbecco's modified Eagle's medium and Ham's F12 mixture, DMEM/F12 • endothelin-1, ET-1 • short circuit current, Isc • Kreb's bicarbonate Ringer, KBR • phosphate-buffered saline, PBS • potential difference, PD This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
