[Effect of bradykinin on airway epithelial ion transport and its modulation by endogenous peptidases].
To elucidate the effect of bradykinin (BK) on airway epithelial ion transport function and its modulation by endogenous peptidases, we studied the electrical properties of canine cultured tracheal epithelium under short-circuited conditions in vitro. Addition of BK to the mucosal side of Ussing chamber increased short-circuit current (SCC) in a dose-dependent manner, the maximal rise from the baseline value (delta SCC max) and the concentration required to produce a half-maximal effect being 7.1 +/- 0.7 microA/cm2 (p < 0.001) and 3.9 +/- 1.0 x 10(-7) M, respectively. This effect was greatly attenuated by the B2-receptor antagonist (D-Arg, Hyp3, Thi5,8, d-Phe7)-BK but not by the B1-receptor antagonist (Des-Arg9, Leu8)-BK. Blockade of angiotensin converting enzyme and aminopeptidase P by captopril and mercaptoethanol did not alter the BK-induced increase in SCC. On the other hand, phosphoramidon and MERGAPTA, inhibitors of neutral endopeptidase and carboxypeptidase N, respectively, strengthened the effect of BK. These results suggest that BK stimulates airway epithelial electrical properties through the activation of B2-receptor subtype, and that endogenous peptidases including neutral nedopeptidase and carboxypeptidase N may play a modulatory role in this action of BK.
Isono
K
K
First Department of Medicine, Tokyo Women's Medical College.
Tamaoki
J
J
Chiyotani
A
A
Konno
K
K
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D001121:Lysine Carboxypeptidase / Q000502:physiology*; D008623:Mercaptoethanol / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
D006020:Glycopeptides; D008623:Mercaptoethanol; D002216:Captopril; D010450:Endopeptidases; D001121:Lysine Carboxypeptidase; D001920:Bradykinin; C008890:phosphoramidon