Effect of GTP on the affinity of denopamine, a new cardiotonic agent, for .BETA.-adrenergic receptors of turkey erythrocytes and rat reticulocyte membranes.
スポンサーリンク
概要
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Affinities of denopamine, a new cardiotonic agent, and several β-adrenergic drugs for turkey erythrocyte membranes (TEM) and rat reticulocyte membranes (RRM) which contain homogeneous β<SUB>1</SUB>- and β<SUB>2</SUB>-receptors, respectively, were studied by receptor binding. The order of potencies of denopamine and several β-adrenergic agonists in displacing <SUP>3</SUP>H-dihydroalprenolol binding (K<SUB>i</SUB>, nM) in TEM was isoproterenol (Iso, 27)>norepinephrine (Nor, 360)>epinephrine (Epi, 860)>dobutamine (DB, 1380)>denopamine (1540)>dopamine (DA, 49500). The order in RRM was Iso (7.3)>Epi (58)>DB (750)>Nor (1090)>denopamine (2300)>DA (26800). In the presence of GTP, competition curves for full agonists like Iso, Epi and Nor shifted to the low affinity side (K<SUB>i</SUB> values increased by 300-500% in TEM and 200-460% in RRM), and the slopes were steepened in both membrane preparations. The K<SUB>i</SUB> value for denopamine increased only in TEM (70%) and that in RRM was not influenced by GTP. This suggests that denopamine has an agonist property at the β<SUB>1</SUB>-receptor but not at the β<SUB>2</SUB>-receptor and that the intrinsic activity at the β<SUB>1</SUB>-receptor of the drug is lower than full agonists. Affinities of DB and DA for TEM were influenced by GTP as well as those for RRM, although the extent of the rightward shift was less than full agonists.
- 公益社団法人 日本薬理学会の論文
著者
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Otsuka Minezo
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
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Ono Yasutoshi
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
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HARIGAYA Shoichi
Biological Research Laboratory : Organic Chemistry Research Laboratory : Tanabe Seiyaku Co., Ltd.
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NAKAJIMA Hiromichi
Biological and Chemical Reseach Labolatories, Tanabe Seiyaka Co., Ltd.
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NAGAO Taku
Biological Research Laboratories, Tauabe Seiyaku Co., Ltd.
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NAKAJIMA Hiromichi
Biological Research Laboratory, Tanabe Selyaku Co., Ltd.
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NAITO Kazuaki
Biological Research Laboratory, Tanabe Selyaku Co., Ltd.
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NAITO Kazuaki
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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HARIGAYA Shoichi
Biological Research Laboratory, Tanabe Selyaku Co., Ltd.
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