title: Comparison of three radioligands for the labelling of human beta-adrenoceptor subtypes.
abstract: We have compared the ability of three radioligands, [(125)I]-cyanopindolol, [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, to label the three human beta-adrenoceptor subtypes. Saturation and competition binding experiments were performed using membrane preparations from Chinese hamster ovary cells stably transfected with the three subtypes. While [(3)H]-CGP 12,177 had very similar affinity for beta(1)- and beta(2)-adrenoceptors (about 40 pM), [(125)I]-cyanopindolol and [(3)H]-dihydroalprenolol had 4- to 6-fold higher affinity for beta(2)- as compared to beta(1)-adrenoceptors (10 vs 45 and 187 vs 1,021 pM, respectively). The affinity of [(125)I]-cyanopindolol at beta(3)-adrenoceptors was considerably lower (440 pM) than at the other two subtypes. The beta(3)-adrenoceptor affinity of [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol was so low that it could not be estimated within the tested range of radioligand concentrations (up to 4,000 pM and 30,000 pM for [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, respectively). We conclude that all three radioligands are ill-suited to label beta(3)-adrenoceptors, particularly in preparations co-expressing multiple subtypes. In the absence of alternatives, [(125)I]-cyanopindolol appears the least unsuitable to label beta(3)-adrenoceptors. There is a need for high-affinity radioligands which are either selective for beta(3)-adrenoceptors or reasonably non-selective among all three beta-adrenoceptor subtypes.
authors.affiliation: Department Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam, The Netherlands.
authors.forename: Nadja
authors.initials: N
authors.lastname: Niclauss
authors.forename: Martina B
authors.initials: MB
authors.lastname: Michel-Reher
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Alewijnse
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004082:Dihydroalprenolol / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D020120:Iodocyanopindolol / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D011412:Propanolamines / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay / Q000379:methods*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007457:Iodine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; C114929:SR 59104A; D013764:Tetrahydronaphthalenes; D014316:Tritium; D004082:Dihydroalprenolol; D020120:Iodocyanopindolol; C033394:CGP 12177