Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update

Critical reappraisal of short-acting bronchodilators for pediatric respiratory diseases

“…SABA acts on β-adrenergic receptors (ARs), a type of postsynaptic receptor coupled to Gs proteins. ARs are classified into three types: β 1, β 2, and β 3, and are stimulated by noradrenalin and adrenaline [ 10 ]. β1-receptors have a high affinity for noradrenaline and adrenaline and can be found in the heart, brain, and adipose tissue.…”

“…β2-Receptors show a lower affinity for noradrenaline and are involved in relaxing vascular and smooth muscles [ 11 ]. Β2-ARs constitute a major population of β-adrenergic receptors within the pulmonary system [ 10 ]. The relative selectivity of β2-agonists on β-ARs explains the systemic side effects caused by β2-agonists (i.e., tachycardia).…”

“…MLCP dephosphorylation of the regulatory myosin light chain (rMLC) ultimately promotes smooth muscle relaxation; ii) Exchange Protein Activated by cAMP (Epac) Pathway: Epac acts as a GEF for Rap GTPases, leading to RhoA downregulation. This reduces rMLC phosphorylation and contributes to ASM relaxation independently of PKA [ 10 ].…”

“…Beyond cAMP, β2AR activation also triggers intracellular Ca 2+ ([Ca 2+ ]i) sequestration, reducing [Ca 2+ ]i dynamics and sensitivity, which further promotes relaxation. Additionally, β2ARs enhance Ca 2+ -activated potassium channels (KCa 2+ ), hyperpolarizing the cell membrane and facilitating bronchodilation [ 10 , 12 ].…”

“…Specificity within this class arises from variations in both the amine group and the benzene ring substitution patterns. These subtle structural modifications significantly impact the pharmacological profile by influencing the interaction with the β2-receptor and leading to differences in potency, duration of action, and selectivity [ 10 ]. The main SABA are listed below.…”