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

• 作者: Robert J. Slack
• 来源期刊: 药理与制药(英文)
• 学科: 医学
• 关键词: β2-Adrenoceptor RADIOLIGAND BINDING Human Lung Tissue BINDING Site
• 年，卷（期）: 2014,（1）
• 页码范围: 30-36
• 页数: 7页
• 分类号: R73

摘要

The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]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 [3H]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 [3H]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 [3H]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 β2-AR.