Salmeterol stimulates β2-adrenoreceptors, which are found in membranes of smooth muscle cells of the bronchi, uterus, gastrointestinal tract, detrusor of the bladder, blood vessels (vessels of skeletal muscles, lungs, coronary vessels). In this case, the smooth muscles of the bronchi relax, the tonus and contractile activity of the myometrium, bladder, gallbladder and bile ducts decrease, motor and stomach and intestine tone, blood vessels expand.
Salmeterol is lipophilic, due to which it not only penetrates well into the membranes of smooth muscle cells of the bronchi, but also lingers in the lipid layer of the membranes, creating a distinctive depot in the immediate vicinity of the receptor. This delays the activation of β2-adrenergic receptors (apparently, a small diffusion rate through the lipid layers of the membrane determines the delayed onset of action of the substance on the receptor and is the cause of the slow development of the drug effect).
Relaxation of smooth muscles with stimulation of β2-adrenoreceptors, conjugated with Gs-proteins stimulating adenylate cyclase, is associated with an increase in the level of cAMP and activation of cAMP-dependent protein kinase in smooth muscle cells. cAMP-dependent protein kinase A inhibits the kinase of light chains of myosin, as a result, phosphorylation of light chains of myosin is disrupted and its interaction with actin does not occur. cAMP-dependent protein kinase A inhibits phospholampane (an inhibitor of Ca2 + -ATPase), as a result in the smooth muscle cells the activity of Ca2 + -ATPase transporting Ca2 + from the cytoplasm to the sarcoplasmic reticulum increases and the concentration of cytoplasmic Ca2 + decreases.All this leads to a decrease in the tone and contractile activity of smooth muscles. It is possible to increase blood glucose levels, since β2-adrenoreceptors control the glycogenolysis process in the liver and skeletal muscles and insulin secretion in the pancreas, and when stimulated they activate phosphorylase and increase the breakdown of glycogen, resulting in increased blood glucose levels.
The secretion of insulin with stimulation of β2-adrenergic receptors is increasing.
The anti-inflammatory effect of fluticasone is due to the interaction with intracellular glucocorticoid receptors-the formation of dimers of the glucocorticoid-glucocorticoid receptor complex (release of the receptor from the bonds with heat shock proteins 70 and 90 and immunophilin). After that, the activated receptor penetrates into the nucleus, binding to glucocorticoid-sensitive regulatory elements of DNA - a specific effect on gene expression (activation and suppression). And interaction with other protein transcription factors, including NFκB and AP-1, which regulate the expression of many proteins of the immune system, leads to suppression of gene expression encoding some cytokines, collagenase and stromelysins.