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

Abstract We characterized the α 1 -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 α 1A -, α 1B - and α 1D -adrenoceptors in hamster ureteral smooth muscle. α 1 -Adrenoceptor antagonists were tested against the phenylephrine (α 1 -adrenoceptor agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach. In the smooth muscle, relative mRNA expression levels for α 1a -, α 1b - and α 1d -adrenoceptors were 10.7%, 1.2% and 88.1%, respectively, and protein expressions were identified for α 1A - and α 1D -adrenoceptors immunohistochemically. Noradrenaline and phenylephrine (α 1 -adrenoceptor agonist) each produced a concentration-dependent tonic contraction, their pD 2 values being 6.87 ± 0.08 and 6.10 ± 0.05, respectively. Prazosin (nonselective α 1 -adrenoceptor antagonist), silodosin (selective α 1A -adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective α 1D -adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA 2 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, α 1A - and α 1D -adrenoceptors were more prevalent than the α 1B -adrenoceptor, with contraction being mediated mainly via α 1A -adrenoceptors. If these findings hold true for humans, α 1A -adrenoceptor antagonists could become useful medication for stone passage in urolithiasis patients.