Mechanical Function and Gene Expression of α1-Adrenoceptor Subtypes in Dog Intravesical Ureter

ObjectivesTo characterize the contractile functions and gene expression of the α1-adrenoceptor (AR) subtypes present in the dog intravesical ureter.MethodsIn a functional study, α1-AR antagonists were evaluated against phenylephrine (α1-AR agonist)-induced contractions in dog isolated intravesical ureteral preparations. The quantitative expression of α1-AR subtype mRNA in this tissue was determined using real-time quantitative reverse transcriptase-polymerase chain reaction.ResultsIn the isolated intravesical ureter, prazosin (nonselective α1-AR antagonist), silodosin (selective α1A-AR antagonist), naftopidil (selective α1D-AR antagonist), and BMY-7378 (selective α1D-AR antagonist) all shifted the concentration-contractile response curve for phenylephrine to the right. The rank order of potencies (pKB value) was silodosin (9.45 ± 0.14), prazosin (8.16 ± 0.08), naftopidil (7.39 ± 0.19), and BMY-7378 (6.78 ± 0.20). The α1A-AR antagonist silodosin was much more potent than the 2 α1D-AR antagonists. The rank order of mRNA expression levels among the α1-AR subtypes was α1d (72.68%), α1a (24.14%), and α1b (3.18%).ConclusionsIn the dog intravesical ureter, α1A-AR plays a major role in contraction, despite the prevalence of α1D-AR.