Pharmacological Modulation of Mucosa-Related Impairment of b-Adrenoceptor-Mediated Relaxation in XXXX Detrusor.

@entity1 @entity9766 @entity5733 @entity11345 @entity10406 @entity3522 @entity7774 @entity1564 @entity150 @entity842 @entity11344 @entity1063 @entity6462 @entity5402
OBJECTIVES: The mucosa of @entity1 detrusor strips impairs @entity5733 -induced relaxation. In order to elucidate which signal transduction pathways are involved in this cross talk between the mucosa and detrusor, we have studied the effects of several pharmacological agonists and antagonists on @entity1063 -mediated relaxation in intact and mucosa-denuded detrusor strips. @entity1 AND METHODS: Strips of detrusor tissue were obtained from @entity1 who had undergone cystectomy for @entity150 and were set up for force measurement. @entity10406 - or @entity5402 -precontracted strips were relaxed with increasing concentrations of @entity1063 in the absence and in the presence of @entity842 synthase inhibitor, @entity6462 ; P2X-receptor antagonist, PPADS; ETA-receptor antagonist, @entity11344 ; ETB-receptor antagonist, @entity11345 ; cyclooxygenase inhibitor, @entity3522 ; AT1-receptor antagonist, @entity1564 ; and @entity9766 antagonist, L-703,606. RESULTS: In intact strips, @entity10406 -stimulated force was enhanced by all blockers; @entity5402 -stimulated force increased with L-703,606. In denuded strips, only @entity6462 augmented the @entity10406 -stimulated contraction. @entity1063 relaxed the precontracted detrusor strips to a significantly larger extent and at lower concentrations in denuded than in intact strips. @entity6462 , PPADS and @entity11344 / @entity11345 had little effect on @entity1063 -induced relaxation, whereas @entity3522 , @entity1564 and L-703,606 sensitized intact @entity5402 -stimulated detrusor strips to @entity1063 -induced relaxation. CONCLUSION: Inhibition of the @entity1063 -induced relaxation of precontracted @entity1 detrusor strips by the mucosa is attenuated by @entity3522 , @entity1564 and L-703,606 suggesting the involvement of prostanoids, @entity7774 and neurokinin pathways. Further experiments are required to unravel the exact mechanisms.
