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, bopindolo l, its two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to beta(1)- and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes us ing the membranes of COS-7 cells transiently expressing beta(1)- and beta(2 )-AR subtypes. Radioligand-binding assays were performed and the re suits w ere compared with those (pKi or pA(2) values) obtained from the membrane-en riched fractions from the rat heart, cerebral cortex, bovine heart, trachea l smooth muscle or guinea-pig heart muscle. The pKi values of pro pranolol, bopindolol, its two metabolites, atenolol, pindolol and metoprolol to beta (1)-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 t o beta-(2)-ARs in COS-7 cell membranes was the same as that of beta(1)-ARs. In addition, good correlations were observed between pKi values of homogen ates from various tissues and those of transfected COS-7 cell membranes to beta(1)- and beta(2)-ARs. Although good correlations were also observed bet ween pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs) and pK i values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low correlation coefficient values to beta(1)-ARs were observed, however. In c onclusion, these results suggested that binding characteristics of H-3-CGP- 12177 to beta-AR subtypes in these membranes from transfected COS-7 cells a re similar to those from membrane fractions of various tissues. Copyright ( C) 2000 S. Karger AG, Basel.