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 beta(1)- and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes using the membranes of COS-7 cells transiently expressing beta(1)- and beta(2)-AR subtypes. Radioligand-binding assays were performed and the results were compared with those (pKi or pA(2) 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 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 to 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 homogenates from various tissues and those of transfected COS-7 cell membranes to beta(1)- and beta(2)-ARs. Although good correlations were also observed between pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs) and pKi values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low correlation coefficient values to beta(1)-ARs were observed, however. In conclusion, these results suggested that binding characteristics of (3)H-CGP-12177 to beta-AR subtypes in these membranes from transfected COS-7 cells are similar to those from membrane fractions of various tissues.
Nakamura
T
T
Department of Pharmacology, Niigata College of Pharmacy, Niigata, Japan.
Suzuki
A
A
Ohnuki
T
T
Hattori
K
K
Watanabe
K
K
Kurose
H
H
Nagao
T
T
Nagatomo
T
T
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002417:Cattle; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D014162:Transfection
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011433:Propranolol; D010869:Pindolol; C036007:bopindolol