Effects of endothelin-1 on epithelial ion transport in human airways.
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.
Blouquit
Sabine
S
Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, Boulogne, France.
Sari
Anouar
A
Lombet
Alain
A
D'herbomez
Michelle
M
Naline
Emmanuel
E
Matran
Regis
R
Chinet
Thierry
T
D000584:Amiloride / Q000494:pharmacology; D001665:Binding Sites; D001692:Biological Transport; D001980:Bronchi / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation; D007477:Ions; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
D019332:Endothelin-1; D007477:Ions; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D015222:Sodium Channels; D002034:Bumetanide; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D002713:Chlorine; D004533:Egtazic Acid; D000584:Amiloride; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin