カテコラミン（CA）代謝物のβ-アドレナリン受容体（β-AR）を介した平滑筋の弛緩作用に及ぼす影響

• Published in: 日本薬理学会年会要旨集 p. 3-P-357
• Main Authors: 八巻, 史子, 小池, 杏奈, 河野, 曜, 張, 瀟月, 吉岡, 健人, 小原, 圭将, 田中, 芳夫
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2020
• Subjects: adrenoceptor; catecholamine; smooth muscle
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.93.0_3-P-357

Effects of CA metabolites on β-AR-mediated relaxation were investigated in mouse (β1)/GP (β2) trachea and rat TA (β3). Among tested seven CA metabolites, metadrenaline (MA) relaxed GP trachea even in the presence of clorgiline (CLG, MAOA inhibitor). In mouse trachea, only in the presence of CLG, normetadrenaline (NMA) and MA significantly inhibited isoprenaline (ISO)-induced relaxation, which was also inhibited by 3,4-dihydroxyphenylglycol (DHPG) in the presence of 3,5-dinitrocatechol (3,5-DNC, COMT inhibitor). In GP trachea, NMA, MA, 3,4-dihydroxymandelic acid (DOMA), and DHPG significantly augmented ISO-induced relaxation, which was inhibited by NMA, and MA in the presence of 3,5-DNC or CLG plus 3,5-DNC, and by DHPG in the presence of 3,5-DNC. In rat TA, DHPG significantly inhibited the relaxation to CGP-12177A (β3-AR partial agonist) in the presence of 3,5-DNC. Our findings indicate that 1) MA may have β2-AR agonistic action; 2) NMA/MA have β1-/β2-AR antagonistic action although they enhance β2-AR-mediated tracheal relaxation in the absence of CA metabolic inhibitors; 3) DHPG shows β1-/β2-/β3-AR antagonistic action, and this is particularly remarkable for β3-AR. Our observations may partly explain some of the pathologies associated with pheochromocytoma, which is characterized by elevated CA metabolites levels.