Effect of endothelin-1 on the serotonin-induced contraction of smooth muscle in the guinea pig trachea.
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.


CONCLUSIONS
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.
Yoshida
M
M
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Aizawa
H
H
Hara
N
N
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology