Expressions and mechanical functions of alpha1-adrenoceptor subtypes in hamster ureter.
We characterized the alpha(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 alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptors in hamster ureteral smooth muscle. alpha(1)-Adrenoceptor antagonists were tested against the phenylephrine (alpha(1)-adrenoceptor agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach. In the smooth muscle, relative mRNA expression levels for alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptors were 10.7%, 1.2% and 88.1%, respectively, and protein expressions were identified for alpha(1A)- and alpha(1D)-adrenoceptors immunohistochemically. Noradrenaline and phenylephrine (alpha(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 alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(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 (3x10(-6) mol/L or more) produced a rightward shift in the concentration-response curve for phenylephrine. Thus, in hamster ureters, alpha(1A)- and alpha(1D)-adrenoceptors were more prevalent than the alpha(1B)-adrenoceptor, with contraction being mediated mainly via alpha(1A)-adrenoceptors. If these findings hold true for humans, alpha(1A)-adrenoceptor antagonists could become useful medication for stone passage in urolithiasis patients.
Tomiyama
Yoshitaka
Y
Pharmacology Research and Development, Kissei Pharmaceutical Co. Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan. yoshitaka_tomiyama@pharm.kissei.co.jp
Kobayashi
Kumi
K
Tadachi
Mariko
M
Kobayashi
Shinya
S
Inada
Yoichi
Y
Kobayashi
Mamoru
M
Yamazaki
Yoshinobu
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014513:Ureter / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
C547719:ADRA1D protein, human; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D010879:Piperazines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C051731:chlorethylclonidine; C095285:silodosin; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine