Multiple mechanisms of bronchoconstrictive responses to endothelin-1.
We investigated the mechanism of the endothelin-1 (ET-1)-induced bronchoconstriction of guinea pig tracheal smooth muscles. ET-1 contracted the tracheas in a dose-dependent manner. A combination of FPL55712 (leukotriene antagonist), diphenhydramine (histamine antagonist), and indomethacin (cyclooxygenase inhibitor) shifted the dose-response curve of ET-1 to the right and suppressed the maximal constriction. Azelastine, an antiallergic agent, exerted essentially similar results. The present data suggest that ET-1 constricts the airway smooth muscles not only by direct action on the tracheal smooth muscles but also by indirect action mediated through production of various chemical mediators in cells other than muscles.
Nomura
A
A
Division of Pulmonary Medicine, University of Tsukuba, Ibaraki, Japan.
Ninomiya
H
H
Saotome
M
M
Ohse
H
H
Ishii
Y
Y
Uchida
Y
Y
Hirata
F
F
Hasegawa
S
S
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004347:Drug Interactions; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010793:Phthalazines / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors
D002867:Chromones; D016232:Endothelins; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D013189:SRS-A; D004155:Diphenhydramine; C006312:FPL 55712; D007213:Indomethacin; C020976:azelastine