title: [Role of bronchodilators in therapy for COPD-mechanisms of LABA and LAMA on airway smooth muscle].
abstract: Long-acting β2-adrenergic receptor agonists (LABAs) and anticholinergics (LAMAs) are widely used clinically as therpy for COPD. Clinical reports have demonstrated that LABAs (salmeterol, formoterol, indacaterol, olodaterol, vilanterol) and LAMAs (tiotropium, glycopyrronium, umeclidinium, aclidinium) are useful to improving symptoms and lung function, and to reducing exacerbation and hospitarization. LABAs expect salmeterol are strong partial agonists, and LAMAs are non-specific antagonists. Ca2+ dynamics and Ca2+ sensitization contribute to relaxation of airway smooth muscle in these bronchodilators. LABAs act on orthosteric and allosteric sites on the β2-adrenergic receptors. In contrast, LAMAs act not only on orthosteric site on the muscarinic receptors, but also allosteric site on the β2-adrenergic receptors, leading to enhancing β2-adrenergic action. Allosteric GPCR modulation is involved in the synergistic effects between LABAs and LAMAs.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kume
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000495:Allosteric Site / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D003692:Delayed-Action Preparations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D043562:Receptors, G-Protein-Coupled; D002118:Calcium