Binding studies of β-adrenoceptor agonists and antagonists in COS-7 cells expressing human β₃-adrenoceptors by radioligand binding assay

The present study reports the assessment of the affinities of some β-adrenoceptor (β-AR) agonists and antagonists like isoproterenol, BRL 37344, bupranolol, SR-59230A, metoprolol, pindolol, propranolol, bopindolol and its two metabolites (18-502 and 20-785) to β₃-AR using the membranes of cloned COS-7 cells by the radioligand binding assay. The β₁- and β₂-AR non-selective antagonists, propranolol and 18-502 showed high affinities to β₃-ARs and the pKi values of propranolol, bopindolol and its two metabolites (18-502 and 20-785) to this subtype were, 7.70, 6.99, 8.03 and 6.48 respectively. The rank order of pKi values for these agents to β₃-ARs in COS-7 cell membranes was, however, different from those to β₁- and β₂-ARs. Only BRL-37344 and SR-59230A tested here, being selective β₃-AR agonist and antagonist respectively, showed higher binding affinity towards β₃-AR of rat white adipose tissue (WAT). Thus. the present study suggests that the non-selective antagonists, propranolol and 18-502, possess the high ability of binding with β₃-AR in cloned COS-7 cells as well as WAT, although different affinities of BRL-37344 and SR-59230A to β₃-AR from those to WAT were observed.