Relative contributions of direct and indirect mechanisms mediating endothelin-induced contraction of @entity840 XXXX .

@entity825 @entity2871 @entity1672 @entity6849 @entity5567 @entity2951 @entity4443 @entity47289 @entity840 @entity1421 @entity7489 @entity2918 @entity8765 @entity112 @entity10125 @entity3352 @entity71362 @entity21313 @entity4756 @entity9077
1. The present study was undertaken to determine the mechanism of action of @entity47289 ( @entity47289 )-induced contraction of the @entity840 isolated @entity825 . 2. @entity47289 (1 nM-0.3 microM) produces a concentration-dependent contraction of @entity840 @entity825 with an EC50 of approximately 25 nM. The combination of the peptidoleukotriene receptor antagonist, SK_F 104353 (10 microM) and the H1- @entity112 receptor antagonist, @entity8765 (10 microM), which abolishes antigen-induced contraction in @entity840 @entity825 , was without effect on @entity47289 concentration-response curves. Furthermore, the @entity71362 antagonist, @entity6849 , (1 or 10 microM) did not inhibit ET-induced contraction. 3. @entity47289 (0.3 microM) did not stimulate @entity112 or immunoreactive peptidoleukotriene release from @entity840 isolated @entity825 . 4. The release of various prostanoids from @entity840 @entity825 was increased significantly by @entity47289 (0.3 microM); the profile of release was @entity1672 (PGD2) = @entity1421 = @entity9077 (PGI2 metabolite) > @entity7489 = PGF2 alpha > 9 alpha, 11 beta PGF2 (PGD2 metabolite). @entity47289 -induced release of @entity2918 , which was about 30% of that elicited by antigen in sensitized tissues, was not affected by epithelium removal and was observed in tissues from which the smooth muscle had been removed. Previous studies in our laboratory indicated that @entity3352 potentiated contraction produced by high concentrations of @entity47289 , whereas a @entity2871 receptor antagonist was without appreciable effect on @entity47289 concentration-response curves. 5. Pretreatment of tissues for 1 h with @entity2951 (10 microM), which depletes different sensory neurones, produced a small, but significant, inhibitory effect on @entity47289 concentration-response curves in the presence but not the absence of the epithelium. The combination of the NK1 @entity4756 receptor antagonist,CP-96,345 (0.1 microM), and the @entity10125 @entity4756 receptor antagonist, @entity21313 (0.1 microM), was without effect on ET-l concentration-response curves but substantially antagonized @entity2951 -induced contraction.6. The present data suggest that in @entity840 isolated @entity825 , ET- 1 produces contraction predominantly via a direct mechanism: there is no significant contribution of the release of @entity112 , @entity4443 , @entity5567 , or @entity4756 (acting on NK1 or @entity10125 receptors). Although @entity47289 evokes the release of an array of @entity2918 from the @entity825 they do not appear to have a major influence on the contractile response.
