Mechanical Function and Gene Expression of α 1-Adrenoceptor Subtypes in Dog Intravesical Ureter

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To characterize the contractile functions and gene expression of the alpha(1)-adrenoceptor (AR) subtypes present in the dog intravesical ureter. In a functional study, alpha(1)-AR antagonists were evaluated against phenylephrine (alpha(1)-AR agonist)-induced contractions in dog isolated intravesical ureteral preparations. The quantitative expression of alpha(1)-AR subtype mRNA in this tissue was determined using real-time quantitative reverse transcriptase-polymerase chain reaction. In the isolated intravesical ureter, prazosin (nonselective alpha(1)-AR antagonist), silodosin (selective alpha(1A)-AR antagonist), naftopidil (selective alpha(1D)-AR antagonist), and BMY-7378 (selective alpha(1D)-AR antagonist) all shifted the concentration-contractile response curve for phenylephrine to the right. The rank order of potencies (pK(B) 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 alpha(1A)-AR antagonist silodosin was much more potent than the 2 alpha(1D)-AR antagonists. The rank order of mRNA expression levels among the alpha(1)-AR subtypes was alpha(1d) (72.68%), alpha(1a) (24.14%), and alpha(1b) (3.18%). In the dog intravesical ureter, alpha(1A)-AR plays a major role in contraction, despite the prevalence of alpha(1D)-AR.