Genomic crosstalk between carbachol, a muscarinic receptor agonist, and the long-acting β-adrenoceptor agonist, indacaterol, in human airway epithelial cells.

Many patients with chronic obstructive pulmonary disease are susceptible to recurrent exacerbations. In this study, we hypothesized that endogenous acetylcholine (ACh) may act as a proinflammatory mediator because long-acting muscarinic receptor antagonists protect against exacerbations, which have an inflammatory basis. This possibility was explored by determining if carbachol (CCh), a stable ACh analog, was a genomic stimulus in BEAS-2B bronchial epithelial cells.

Comparison of the Genomic Activity of an EP-Receptor and β-Adrenoceptor Agonist in BEAS-2B Human Bronchial Epithelial Cells: In Search of Compartmentalized, cAMP-Dependent Gene Expression.

It has been proposed that inhaled E-prostanoid 4 (EP)-receptor agonists could represent a new class of bronchodilators for the treatment of asthma that are as effective as -adrenoceptor agonists. However, the genomic impact of such drugs is unknown despite being potentially deleterious to respiratory health. Herein, we used mRNA-seq to compare the transcriptomic responses produced by 2-[3-[(1R,2S,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-5-[2-(methoxymethyl)phenyl]pent-1-enyl]-5-oxo-cyclopentyl]sulphanylpropylsulphanyl] acetic acid (ONO-AE1-329; an EP-receptor agonist) and vilanterol (a -adrenoceptor agonist) in BEAS-2B human airway epithelial cells.

The β-Blocker Carvedilol and Related Aryloxypropanolamines Promote ERK1/2 Phosphorylation in HEK293 Cells with Values Distinct From Their Equilibrium Dissociation Constants as -Adrenoceptor Antagonists: Evidence for Functional Affinity.

The determination of affinity by using functional assays is important in drug discovery because it provides a more relevant estimate of the strength of interaction of a ligand to its cognate receptor than radioligand binding. However, empirical evidence for so-called, "functional affinity" is limited. Herein, we determined whether the affinity of carvedilol, a -adrenoceptor antagonist used to treat heart failure that also promotes extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, differed between these two pharmacological activities.