title: Endothelin-1 stimulates chloride secretion across canine tracheal epithelium.
abstract: Although much attention has been paid to the effect of endothelin on the bronchopulmonary system, there are few reports concerning the effect of endothelin on Cl- secretion across airway epithelium. We examined the effects of endothelin-1, -2 and -3 on bioelectric parameters of canine tracheal epithelium, a tissue in which Cl- is actively secreted and Na+ is absorbed. Potential difference (PD) and short-circuit current (SCC) were measured using an Ussing chamber with 0.5 cm2 of exposed area, and conductance (G) was calculated by dividing SCC by PD. Luminal endothelin-1 produced transient increases in PD and SCC, returning to baseline values within 5 min after stimulation in a dose-dependent fashion and reached mean responses of 123 and 126% of baseline PD and SCC, respectively, at 10(-6) M of endothelin-1, whereas submucosal endothelin-1 did not alter PD and SCC. G remained unchanged when stimulated by endothelin-1. Endothelin-2 and -3 did not produce any significant alterations in PD and SCC. Endothelin-1 evoked increases in PD and SCC, which were not altered by pretreatment with luminal amiloride (10(-4) M), or by treatment with submucosal propranolol (10(-5) M). Ionic substitution of Cl- with nontransported anions, iodide and gluconate, inhibited endothelin-1-induced increases in PD and SCC. Pretreatment with 10(-5) M indomethacin partially inhibited Endothelin-1-evoked increases in PD and SCC. These findings indicate that endothelin-1 stimulates Cl- secretion partially through the generation of cyclooxygenase products of arachidonic acid.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: S
authors.initials: S
authors.lastname: Shimura
authors.forename: H
authors.initials: H
authors.lastname: Ishihara
authors.forename: M
authors.initials: M
authors.lastname: Nagaki
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Takishima
mesh_terms: D000584:Amiloride; D000818:Animals; D002712:Chlorides / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D016232:Endothelins / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016623:Ion Pumps / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D014132:Trachea / Q000502:physiology*
chemical_list: D002712:Chlorides; D016232:Endothelins; D016623:Ion Pumps; D010042:Ouabain; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D007213:Indomethacin