AJP - Lung Cellular and Molecular Physiology, Vol 261, Issue 2 188-L194, Copyright © 1991 by American Physiological Society

ARTICLES

Endothelin stimulates chloride secretion across canine tracheal epithelium

P. I. Plews, Z. A. Abdel-Malek, C. A. Doupnik and G. D. Leikauf
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0182.

The endothelins (ET) are a group of isopeptides produced by a number of cells, including canine tracheal epithelial cells. Because these compounds are endogenous peptides that may activate eicosanoid metabolism, we investigated the effects of ET on Cl secretion in canine tracheal epithelium. Endothelin 1 (ET-1) was found to produce a dose-dependent change in short-circuit current (Isc) that increased slowly and reached a maximal value within 10-15 min. When isopeptides of ET were compared, 300 nM ET-1 and ET-2 produced comparable maximal increases in Isc, whereas ET-3 produced smaller changes in Isc (half-maximal concentrations of 2.2, 7.2, and 10.4 nM, respectively). Ionic substitution of Cl with nontransported anions, iodide and gluconate, reduced ET-1-induced changes in Isc. Furthermore, the response was inhibited by the NaCl cotransport inhibitor, furosemide. In paired tissues, ET-1 significantly increased mucosal net 36Cl flux without significant effect on 22Na flux. The increase in Isc induced by ET was diminished by pretreatment with indomethacin. The second messengers mediating the increase in Isc were investigated in cultured canine tracheal epithelial cells. ET-1 stimulated the release of [3H]arachidonate from membrane phospholipids, increased intracellular Ca2+ (occasionally producing oscillations), and increased adenosine 3',5'-cyclic monophosphate accumulation. The latter was diminished by indomethacin. Thus ET is a potent agonist of Cl secretion (with the isopeptides having the following potency: ET-1 greater than or equal to ET-2 greater than ET-3) and acts, in part, through a cyclooxygenase-dependent mechanism.

This article has been cited by other articles:

				M. C. Okafor and N. A. Delamere The Inhibitory Influence of Endothelin on Active Sodium-Potassium Transport in Porcine Lens Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 1018 - 1023. [Abstract] [Full Text]

				H. Oonuma, T. Nakajima, T. Nagata, K. Iwasawa, Y. Wang, H. Hazama, Y. Morita, Y. Wang, K. Yamamoto, R. Nagai, et al. Endothelin-1 Is a Potent Activator of Nonselective Cation Currents in Human Bronchial Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 213 - 221. [Abstract] [Full Text]

				H. Ninomiya, T. Inui, and T. Masaki Paracrine Endothelin Signaling in the Control of Basal Cell Proliferation in Guinea Pig Tracheal Epithelium J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 469 - 480. [Abstract] [Full Text]

				H. Yoshimura, J. Nishimura, C. Sakihara, S. Kobayashi, S. Takahashi, and H. Kanaide Expression and Function of Endothelins, Endothelin Receptors, and Endothelin Converting Enzyme in the Porcine Trachea Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 471 - 480. [Abstract] [Full Text]