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English: Figure 2. Molecular interactions involving the mechanisms of action of indacaterol, glycopyrronium and mometasone furoate. Indacaterol binds to the β2-adrenergic receptor (β2-AR), thus sequentially activating the stimulatory Gs protein and adenylyl cyclase (AC), which is responsible for cAMP synthesis and the subsequent activation of cAMP-dependent protein kinase A (PKA). This signaling pathway not only leads to bronchodilatation, but also promotes GR nuclear translocation, thus potentiating the pharmacologic effects of corticosteroids. The latter in turn increase β2-AR mRNA levels via GRE-dependent stimulation of β2-AR gene transcription. IND-induced bronchodilatation is synergistically potentiated by GLY through a competitive antagonism of M2 and M3 muscarinic receptors. With respect to the blockade of the M2 receptor coupled to AC inhibition operated by the inhibitory G protein (Gi), GLY occupies for a much longer time the M3 receptor, whose stimulation is the main mechanism underlying acetylcholine-induced bronchoconstriction, mediated by M3-coupling to Gq protein and phospholipase C (PLC). The latter enzyme catalyzes the generation of the intracellular second messenger inositol trisphosphate (IP3) that elicits airway smooth muscle contraction via mobilization of cytosolic calcium ions.