The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-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 β2-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 β1-antagonist) inhibited the relaxant action of BDTI with pK(B) 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 K(d) values of radioligand ([3H]-CGP12177) were 453.3 ± 30.8 and 563.4 ± 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the B(max) 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 (K(i) 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (K(i) 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 K(i) (heart)/K(i) (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.
|Number of pages||9|
|Publication status||Published - Jul 1996|
- β-adrenoceptor agonist
- Tracheal smooth muscle cells
ASJC Scopus subject areas