Expressions and mechanical functions of α1-adrenoceptor subtypes in hamster ureter

We characterized the α1-adrenoceptor subtypes in hamster ureters according to gene and protein expressions and contractile function. Real-time quantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis were performed to determine mRNA levels and receptor protein expressions respectively, for α1A-, α1B- and α1D-adrenoceptors in hamster ureteral smooth muscle. α1-Adrenoceptor antagonists were tested against the phenylephrine (α1-adrenoceptor agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach. In the smooth muscle, relative mRNA expression levels for α1a-, α1b- and α1d-adrenoceptors were 10.7%, 1.2% and 88.1%, respectively, and protein expressions were identified for α1A- and α1D-adrenoceptors immunohistochemically. Noradrenaline and phenylephrine (α1-adrenoceptor agonist) each produced a concentration-dependent tonic contraction, their pD2 values being 6.87 ± 0.08 and 6.10 ± 0.05, respectively. Prazosin (nonselective α1-adrenoceptor antagonist), silodosin (selective α1A-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective α1D-adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA2 values, 8.60 ± 0.07, 9.44 ± 0.06 and 5.75 ± 0.07, respectively). Chloroethylclonidine (3 × 10− 6 mol/L or more) produced a rightward shift in the concentration–response curve for phenylephrine. Thus, in hamster ureters, α1A- and α1D-adrenoceptors were more prevalent than the α1B-adrenoceptor, with contraction being mediated mainly via α1A-adrenoceptors. If these findings hold true for humans, α1A-adrenoceptor antagonists could become useful medication for stone passage in urolithiasis patients.