オバラ　ケイスケ   Obara Keisuke   小原　圭将    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Pharmacological identification of β-adrenoceptor subtypes mediating isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle
掲載誌名	正式名：Journal of Smooth Muscle Research 略　 称：J Smooth Muscle Res ISSNコード：0916-8737/1884-8796
掲載区分	国内
出版社	Japan Society of Smooth Muscle Research
巻・号・頁	54,pp.13-27
著者・共著者	Chino D†, Sone T†, Yamazaki K†, Tsuruoka Y†, Yamagishi R†, Shiina S†, Obara K†, Yamaki F†, Higai K†, Tanaka Y＊†
発行年月	2018/03
概要	Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10-7 M). Atenolol (a selective β1-AR antagonist; 3 × 10-7–10-6 M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA2 value was calculated to be 6.49 (95% confidence interval: 6.34–6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β2-AR antagonist) at 10-9–10-8 M, but was competitively antagonized by 10-7–3 × 10-6 M, with a pA2 value of 7.41 (95% confidence interval: 7.18–8.02). In the presence of propranolol (3 × 10-7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA2 value of 5.90 (95% confidence interval: 5.73–6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β1-AR and β3-AR.