Tracheal Relaxing Effects and .BETA.2-Selectivity of TA-2005, a Newly Developed Bronchodilating Agent, in Isolated Guinea Pig Tissues.
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概要
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Tracheal relaxing effects and β<SUB>2</SUB>-selectivity of TA-2005 were investigated by functional experiments and radioligand binding assay in guinea pigs in comparison with those of other β-agonists, isoproterenol, procaterol, formoterol and salbutamol. The relaxing activity of TA-2005 on histamine-induced contraction in the isolated trachea was most potent among the five agonists, and it was blocked by a β<SUB>2</SUB>-selective antagonist (ICI 118, 551) but not by a β<SUB>1</SUB>-selective antagonist (bisoprolol). The potency of the relaxing effect was in the order of TA-2005 (pD<SUB>2</SUB> = 9.79) > for moterol > procaterol > isoproterenol > salbutamol. The positive chronotropic effect of TA-2005 was similar to that of isoproterenol; and it was more potent than those of formoterol, procaterol and salbutamol in the isolated atria. The selectivity for tracheal muscle to atria of these agonists were in the order of procaterol ≥ formoterol > TA-2005 > salbutamol >> isoproterenol. A radioligand binding experiment using guinea pig lung and cardiac ventricle as β<SUB>2</SUB>- and β<SUB>1</SUB>-adrenoceptor sources, respectively, has also demonstrated that TA-2005 possesses extremely high affinity (IC<SUB>50</SUB> = 1.04 nM) and selectivity (38-fold) to β<SUB>2</SUB>-adrenoceptors. By addition of GTP, the competition curve of [<SUP>125</SUP>I]iodocyanopindolol shifted rightward, indicating the agonist property. These results confirmed that TA-2005 is a highly β<SUB>2</SUB>-selective agonist that exerts a potent tracheal relaxing effect.
- 公益社団法人 日本薬理学会の論文
著者
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IKEZAWA Katsuo
Biological and Chemical Reseach Labolatories, Tanabe Seiyaka Co., Ltd.
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NAITO Kazuaki
Biological Research Laboratory, Tanabe Selyaku Co., Ltd.
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Kikkawa Hideo
Biological Research Laboratory, Tanahe Seiyaku Co., Ltd.
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NAITO Kazuaki
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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Naito Kazuaki
Biological Research Laboratory, Tanahe Seiyaku Co., Ltd.
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Ikezawa Katsuo
Biological Research Laboratory, Tanahe Seiyaku Co., Ltd.
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