Angiotensin II-1 receptor-mediated Cl secretion by canine tracheal epithelium.
To elucidate the effect of angiotensin II (AII) on ion transport function of airway epithelium, we studied the bioelectrical properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of AII to submucosal solution in Ussing chambers increased the short-circuit current (ISC) in a dose-dependent fashion, the maximal increase from the baseline value and the concentration required to produce a half-maximal effect being 5.2 +/- 0.5 microA/cm2 (p < 0.001) and 10(-6) M, respectively. In contrast, mucosal AII had little effect. The AII-induced increase in ISC was not altered by the AII-2 receptor antagonist EXP655 but was depressed by the AII-1 receptor antagonist DuP 753. Diphenylamine-2-carboxylate, Cl-free medium, indomethacin, the phospholipase A2 inhibitor mepacrine, and the methyltransferase inhibitor 3-deazaadenosine reduced the change in ISC, whereas amiloride and the lipoxygenase inhibitor AA-861 did not. Addition of AII to the submucosal but not the mucosal side increased the release of prostaglandin E2, an effect that was abolished by DuP 753. These results suggest that AII may interact with the submucosal AII-1 receptor and stimulate Cl secretion across tracheal epithelium through the mobilization of arachidonic acid and the release of prostaglandin E2.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Isono
K
K
Chiyotani
A
A
Kondo
M
M
Konno
K
K
D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003172:Complement C1 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011945:Receptors, Angiotensin / Q000145:classification / Q000187:drug effects; D014132:Trachea / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D003172:Complement C1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015232:Dinoprostone