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
言語種別	英語
発表タイトル	The β1- and β3-adrenoceptor-mediated relaxation induced by isoprenaline in guinea pig colonic longitudinal smooth muscle
会議名	Adrenoceptors 2018
主催者	Martin C. Michel, Johannes Gutenberg University, Mainz, Germany
学会区分	国際学会
発表形式	口頭
講演区分	シンポジウム・ワークショップ パネル（その他）
発表者・共同発表者	◎Obara K†, Chino D†, Sone T†, Yamazaki K†, Tsuruoka Y†, Yamagishi R†, Shiina S†,Yamaki F†, Higai K†, Tanaka Y†
発表年月日	2018/06/29
開催地 （都市, 国名）	Shizuoka, Japan (Granship Convention Center)
学会抄録	10th Adrenoceptor Symposium, Receptor Structure Changes the Pharmacology Paradigm, Participant Booklet 11-12
概要	Object: This study was carried out to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline (ISO)-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 (ISO, adrenaline (AD), and noradrenaline (NA)). In addition, we investigated the inhibitory effect of subtype-selective β-AR antagonists on ISO-induced relaxation. Furthermore, total RNA was extracted from colonic longitudinal smooth muscles and the mRNA expression of β-AR subtypes was examined using RT-PCR method. Results: Expression of mRNAs for all β-AR subtypes (β1–β3) was detected in guinea pig colonic longitudinal smooth muscle. In the absence of propranolol (a non-selective β-AR antagonist), the relaxant potencies of the catecholamines were ranked as: ISO > NA ≈ AD, whereas the rank order was ISO > NA > AD in the presence of propranolol (3 × 10-7 M). Atenolol (a selective β1-AR antagonist; 3 × 10-7–10-6 M) competitively antagonized ISO-induced relaxation, and the pA2 value was calculated to be 6.49 (95% confidence interval: 6.34–6.83). Although the relaxation to ISO 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 × 10-7 M, with a pA2 value of 7.41 (95% confidence interval: 7.18–8.02). In the presence of propranolol (3 × 10-7 M), bupranolol (a non-selective β-AR antagonist) competitively antagonized ISO-induced relaxation, and the pA2 value was calculated to be 5.90 (95% confidence interval: 5.73–6.35). Conclusion: These findings indicated that the β1- and β3-AR are primarily β-AR subtypes involved in ISO-induced relaxation in colonic longitudinal guinea pig muscles.