title: The role of a low beta 1-adrenoceptor selectivity of [3H]CGP-12177 for resolving subtype-selectivity of competitive ligands.
abstract: On the basis of saturation binding studies on rat cardiac microsomes, which contained a mixed population of beta-adrenoceptor subtypes, [3H]CGP-12177 is presumed to be a non-selective beta-adrenergic radioligand. However, saturation binding studies carried out in the presence of subtype-saturating concentrations of the beta 2-selective antagonist ICI 118,551 and the beta 1-selective antagonist ICI 89,406, respectively, revealed a KD for beta 1-adrenoceptors of 0.33 +/- 0.02 nmol/l and a KD for beta 2-adrenoceptors of 0.90 +/- 0.14 nmol/l. Competition experiments with the highly selective antagonists revealed greatly different competition binding curves in the presence of either [3H]CGP-12177 or (-)[125I]iodocyanopindolol (ICYP), a beta-adrenergic radioligand considered to be as non-selective as [3H]CGP-12177. The following results are further suggestive for a selectivity of [3H]CGP-12177 for beta 1-adrenoceptors: (1) Using non-linear regression analysis, a significantly lower selectivity (expressed as the ratio of the IC50 for beta 2-adrenoceptors to the IC50 for beta 1-adrenoceptors) as well as a larger proportion of beta 1-adrenoceptors were calculated by competition of the beta 1-selective antagonist ICI 89,406 with [3H]CGP-12177 binding than by competition of ICI 89,406 with ICYP binding; (2) reducing the [3H]CGP-12177 concentration from 2 to 0.4 nmol/l, competition experiments with ICI 89,406 led to an increase in the estimated selectivity of the competitor and in the estimated proportion of beta 1-adrenoceptors; (3) reverse findings were obtained with ICI 118,551, a beta 2-selective antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D020120:Iodocyanopindolol; D008861:Microsomes / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; C025716:ICI 89406; C033394:CGP 12177