TY - JOUR
T1 - Pharmacological characteristics of bdti, a new isoquinoline-derived β2-adrenoceptor agonist, in canine trachea and rat heart
AU - Lin, Chien Huang
AU - Yang, Chuen Mao
AU - Chen, Chi Ming
AU - Ko, Feng Nien
AU - Teng, Che Ming
PY - 1996/1/1
Y1 - 1996/1/1
N2 - The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-di-hydroxy-1,2,3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other β-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 ± 0.08) > BDTI (6.11 ± 0.06) ≃ salbutamol (6.14 ± 0.08). ICI-118,551 (a selective β2-antagonist) and atenolol (a selective βι-antagonist) inhibited the relaxant action of BDTI with pKB values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The Kd values of radioligand ([3H]-CGP 12177) were 45 3.3 ± 30.8and 563.4 ± 96.7pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the Bmax values were 64.6 ± 10.7 and 245.7 ± 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (Ki 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (Ki 2.76 ± 0.36, 2.31 ± 0.26 and 0.22 ± 0.03 μmol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to β2-adrenoceptors as judged from the Ki (heart)/Kj (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 ± 0.2 and 0.4 ± 0.1 μmol/l, respectively) and rat cardiomyocytes (EC50 6.2 ± 0.5 and 5.7 ± 0.6 μmol/l, respectively). The selectivity of BDTI and salbutamol for β2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a β2- selective adrenoceptor agonist.
AB - The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-di-hydroxy-1,2,3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other β-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 ± 0.08) > BDTI (6.11 ± 0.06) ≃ salbutamol (6.14 ± 0.08). ICI-118,551 (a selective β2-antagonist) and atenolol (a selective βι-antagonist) inhibited the relaxant action of BDTI with pKB values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The Kd values of radioligand ([3H]-CGP 12177) were 45 3.3 ± 30.8and 563.4 ± 96.7pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the Bmax values were 64.6 ± 10.7 and 245.7 ± 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (Ki 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (Ki 2.76 ± 0.36, 2.31 ± 0.26 and 0.22 ± 0.03 μmol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to β2-adrenoceptors as judged from the Ki (heart)/Kj (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 ± 0.2 and 0.4 ± 0.1 μmol/l, respectively) and rat cardiomyocytes (EC50 6.2 ± 0.5 and 5.7 ± 0.6 μmol/l, respectively). The selectivity of BDTI and salbutamol for β2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a β2- selective adrenoceptor agonist.
KW - BDTI
KW - Cardiomyocytes
KW - Tracheal smooth muscle cells
KW - β-Adrenoceptor agonist
UR - http://www.scopus.com/inward/record.url?scp=0029816412&partnerID=8YFLogxK
U2 - 10.1159/000139411
DO - 10.1159/000139411
M3 - 文章
C2 - 8875598
AN - SCOPUS:0029816412
SN - 0031-7012
VL - 53
SP - 19
EP - 27
JO - Pharmacology
JF - Pharmacology
IS - 1
ER -