タナカ ヨシオ   Tanaka Yoshio
  田中 芳夫
   所属   東邦大学  薬学部 薬学科
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Noradrenaline-induced relaxation of urinary bladder smooth muscle is primarily triggered through the β₃-adrenoceptor in rats
掲載誌名 正式名:Biological & Pharmaceutical Bulletin
略  称:BPB
ISSNコード:09186158
掲載区分国内
出版社 Bulletins of the Pharmaceutical Society of Japan
巻・号・頁 42(5),pp.736-743
著者・共著者 Obara K†, Suzuki S†, Shibata H†, Yoneyama N†, Hamamatsu S†, Yamaki F†, Higai K†, Tanaka Y*†
担当区分 最終著者,責任著者
発行年月 2019/05
概要 β-Adrenoceptors are subclassified into three subtypes (β1–β3). Among these, β3-adrenoceptors are present in various types of smooth muscle and are believed to play a role in relaxation responses of these muscles. β3-Adrenoceptors are also present in urinary bladder smooth muscle (UBSM), although their expression varies depending on the animal species. To date, there has been little information available about the endogenous ligand that stimulates β3-adrenoceptors to produce relaxation responses in UBSM. In this study, to determine whether noradrenaline is a ligand of UBSM β3-adrenoceptors, noradrenaline-induced relaxation was analyzed pharmacologically using rat UBSM. We also assessed whether noradrenaline metabolites were ligands in UBSM. In isolated rat urinary bladder tissues, mRNAs for β1-, β2-, and β3-adrenoceptors were detected using reverse transcription polymerase chain reaction. In UBSM preparations contracted with methacholine (3 × 10−5 M), noradrenaline-induced relaxation was not inhibited by the following antagonists: atenolol (10−6 M; selective β1-adrenoceptor antagonist), ICI-118,551 (3 × 10−8 M; selective β2-adrenoceptor antagonist), propranolol (10−7 M; non-selective β-adrenoceptor antagonist), and bupranolol (10−7 M; non-selective β-adrenoceptor antagonist). In the presence of propranolol (10−6 M), noradrenaline-induced relaxation was competitively inhibited by bupranolol (3 × 10−7–3 × 10−6 M) or SR59230A (10−7–10−6 M; selective β3-adrenoceptor antagonist), with their pA2 values calculated to be 6.64 and 7.27, respectively. None of the six noradrenaline metabolites produced significant relaxation of methacholine-contracted UBSM. These findings suggest that noradrenaline, but not its metabolites, is a ligand for β3-adrenoceptors to produce relaxation responses of UBSM in rats.