TITLE:
Evidence for a Non-β2-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of β2-Adrenoceptor Agonists
AUTHORS:
Robert J. Slack
KEYWORDS:
β2-Adrenoceptor; Radioligand Binding; Human Lung; Tissue Binding Site
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.1,
January
9,
2014
ABSTRACT: 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 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.