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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Beta-3 adrenoceptor selectivity of the dioxolane dicarboxylate phenethanolamines.

The beta-1, beta-2 and beta-3 adrenergic properties of several benzodioxole-containing phenethanolamines were determined in vitro in both functional and binding assays. In addition, two of the compounds were evaluated for their effects on radioligand binding and cyclic AMP (cAMP) production in stably transfected Chinese Hamster Ovary (CHO) cells expressing the cloned rat or human beta-3 adrenoceptor or the human beta-2 or beta-1 adrenoceptor. The (+/-)-R*,R*-racemate, CL 314,514, and the pure (-)-R,R enantiomer, CL 316,243, stimulated rat adipocyte lipolysis (beta-3 effect) with EC50 values in the low nanomolar range, while having no effect on the rate of contraction of guinea pig atria (beta-1 effect) and little or no ability to prevent the insulin-stimulated incorporation of [14C]glucose into rat soleus muscle glycogen (beta-2 effect) with concentrations as great as 100 microM. The lack of beta-1 and beta-2 adrenergic activity was confirmed by the low affinity of the compounds for beta-1 or beta-2 adrenoceptors in plasma membranes from rat heart or rat soleus muscle, respectively. In CHO cells expressing each human beta adrenoceptor subtype, CL 314,514 bound to beta-3-CHO cells with a Ki of 2 microM and stimulated cAMP production with an activation constant (Kact) of 1 microM, whereas it did not bind to either beta-1- or beta-2-CHO cells at 100 microM. CL 316,243 bound to membranes from rat beta-3-CHO cells with a Ki of 1 microM and stimulated cAMP production in beta-3-CHO cells with a Kact of 0.7 nM.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Beta-3 adrenoceptor selectivity of the dioxolane dicarboxylate phenethanolamines. Dolan, J.A., Muenkel, H.A., Burns, M.G., Pellegrino, S.M., Fraser, C.M., Pietri, F., Strosberg, A.D., Largis, E.E., Dutia, M.D., Bloom, J.D. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
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