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

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Abstract

We have compared the ability of three radioligands, [125I]-cyanopindolol, [3H]-CGP 12,177 and [3H]-dihydroalprenolol, to label the three human β-adrenoceptor subtypes. Saturation and competition binding experiments were performed using membrane preparations from Chinese hamster ovary cells stably transfected with the three subtypes. While [3H]-CGP 12,177 had very similar affinity for β1- and β2-adrenoceptors (about 40 pM), [125I]-cyanopindolol and [3H]-dihydroalprenolol had 4- to 6-fold higher affinity for β2- as compared to β1-adrenoceptors (10 vs 45 and 187 vs 1,021 pM, respectively). The affinity of [125I]-cyanopindolol at β3-adrenoceptors was considerably lower (440 pM) than at the other two subtypes. The β3-adrenoceptor affinity of [3H]-CGP 12,177 and [3H]-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 [3H]-CGP 12,177 and [3H]-dihydroalprenolol, respectively). We conclude that all three radioligands are ill-suited to label β3-adrenoceptors, particularly in preparations co-expressing multiple subtypes. In the absence of alternatives, [125I]-cyanopindolol appears the least unsuitable to label β3-adrenoceptors. There is a need for high-affinity radioligands which are either selective for β3-adrenoceptors or reasonably non-selective among all three β-adrenoceptor subtypes.

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Acknowledgement

We thank Dr. Carsten Hoffmann (University of Würzburg, Germany) for providing the CHO cells.

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Authors and Affiliations

  1. Department Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    Nadja Niclauß, Martina B. Michel-Reher, Astrid E. Alewijnse & Martin C. Michel

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  1. Nadja Niclauß
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  2. Martina B. Michel-Reher
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  3. Astrid E. Alewijnse
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  4. Martin C. Michel
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Correspondence to Martin C. Michel.

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Niclauß, N., Michel-Reher, M.B., Alewijnse, A.E. et al. Comparison of three radioligands for the labelling of human β-adrenoceptor subtypes. Naunyn-Schmied Arch Pharmacol 374, 99–105 (2006). https://doi.org/10.1007/s00210-006-0104-z

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  • DOI: https://doi.org/10.1007/s00210-006-0104-z

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