Assessment of affinities of propranolol and bopindolol to membranes from COS-7 cell transiently transfected with beta-1-and beta-2-adrenoceptors using a radioligand-binding assay method

This study was performed to assess the affinities of propranolol, bopindolol, its two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to β₁- and β₂-adrenoceptor (β- and β₂-AR) subtypes using the membranes of COS-7 cells transiently expressing β₁- and β₂-AR subtypes. Radioligand-binding assays were performed and the results were compared with those (pKi or pA₂ values) obtained from the membrane-enriched fractions from the rat heart, cerebral cortex, bovine heart, tracheal smooth muscle or guinea-pig heart muscle. The pKi values of propranolol, bopindolol, its two metabolites, atenolol, pindolol and metoprolol to β₁-AR subtypes obtained from COS-7 cell membranes were 9.02 ± 0.04, 7.44 ± 0.12, 9.38 ± 0.31, 6.65 ± 0.16, 5.55 ± 0.14, 8.17 ± 0.15 and 5.99 ± 0.13, respectively. The rank order of pKi values for these agents to β-₂-ARs in COS-7 cell membranes was the same as that of β₁-ARs. In addition, good correlations were observed between pKi values of homogenates from various tissues and those of transfected COS-7 cell membranes to β₁- and β₂-ARs. Although good correlations were also observed between pA₂ values obtained from tracheal smooth muscle (β₂-ARs) and pKi values obtained from transfected COS-7 cell membranes to β₂-ARs, low correlation coefficient values to β₁-ARs were observed, however. In conclusion, these results suggested that binding characteristics of ³H-CGP-12177 to β-AR subtypes in these membranes from transfected COS-7 cells are similar to those from membrane fractions of various tissues. (C) 2000 S. Karger AG, Basel.