Evidence for a Non-<i>β</i><sub>2</sub>-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of <i>β</i><sub>2</sub>-Adrenoceptor Agonists
- 1 Respiratory TAU Biology, GlaxoSmithKline, Stevenage, UK.
Abstract
The aim of this study was to compare the binding profile of a range of β 2 -adrenoceptor ( β 2 -AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β 2 -AR antagonist ([ 3 H]propranolol) or agonist ([ 3 H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[ β , γ -imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [ 3 H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [ 3 H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [ 3 H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β 2 -AR.
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