Comparison of three radioligands for the labelling of human beta-adrenoceptor subtypes

Naunyn Schmiedebergs Arch Pharmacol. 2006 Nov;374(2):99-105. doi: 10.1007/s00210-006-0104-z. Epub 2006 Oct 7.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / metabolism
  • Adrenergic beta-Antagonists / metabolism
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dihydroalprenolol / metabolism
  • Ethanolamines / metabolism
  • Humans
  • Iodine Radioisotopes / metabolism
  • Iodocyanopindolol / metabolism
  • Isotope Labeling / methods
  • Kinetics
  • Propanolamines / metabolism
  • Protein Binding
  • Radioligand Assay / methods*
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Adrenergic, beta-3 / genetics
  • Receptors, Adrenergic, beta-3 / metabolism
  • Tetrahydronaphthalenes / metabolism
  • Tritium / metabolism

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Ethanolamines
  • Iodine Radioisotopes
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • SR 59104A
  • Tetrahydronaphthalenes
  • Tritium
  • Dihydroalprenolol
  • Iodocyanopindolol
  • CGP 12177