Background: Endothelin (ET), a potent constrictor of smooth muscle including that of the airways, may contribute to the development of airway hyperresponsiveness. Objective: To investigate the role of ET-1 on the airway smooth muscle, we examined the effects of ET-1 on the serotonin-induced contraction of guinea pig tracheal smooth muscle. Methods: The changes in isometric tension evoked by serotonin were measured before and after the application of a subthreshold dose (a dose which did not induce smooth muscle contraction by itself) of ET-1. Results: Serotonin caused smooth muscle contraction in a dose-dependent manner. The subthreshold doses of ET-1 (1 pM) and sarafotoxin 6c (1 pM), a selective ETB receptor agonist, were found to potentiate significantly the contraction induced by serotonin. A potentiating effect of ET-1 was not altered by indomethacin or calphostin C, a protein kinase C inhibitor. Conclusion: These results suggest that a subthreshold concentration of ET-1 can potentiate serotonin-induced contraction of smooth muscle through the activation of ETB receptor, while in contrast cyclooxygenase and protein kinase C were found not to be involved in this mechanism.

Keywords:
Endothelin-1, Serotonin, Smooth muscle contraction, Trachea, Protein kinase C
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1999
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