Beta2-agonist and anticholinergic drugs in the treatment of lung disease.
The lungs are innervated by both the sympathetic and parasympathetic nervous systems, which entails the activation of adrenergic and muscarinic receptors, respectively. Both the adrenergic and muscarinic receptors are G-protein-coupled receptors, and they share many similar signal transduction molecules. These receptors are widely expressed in the lung and the specific receptor expression can vary among the species. The location and the subtype of receptor expressed are important in the regulation of normal airway function. Acetylcholine released from the parasympathetic fibers activates the M3 muscarinic receptors located on the airway smooth muscle, causing bronchoconstriction. To counter this activity, M2 muscarinic receptors located on the parasympathetic nerves inhibit release of acetylcholine. Beta2-adrenergic receptors are expressed on the airway smooth muscle where activation causes bronchodilation. Adrenergic receptors are also on the autonomic nerves where they can modulate neurotransmitter release. The crosstalk between these G-protein-coupled receptors and downstream pathways ensures normal airway function. The prejunctional and postjunctional muscarinic and adrenergic receptors control autonomic tone and any imbalance or selective blockade of the receptors can compromise the system and cause the airways to become hyperreactive. The location, function, and crosstalk of the adrenergic and muscarinic receptors must be considered in the design, development, and use of drugs to combat airway diseases.
Proskocil
Becky J
BJ
Physiology and Pharmacology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, MC L334, Portland, OR 97239, USA.
Fryer
Allison D
AD
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000502:physiology / Q000503:physiopathology; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000294:innervation / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009130:Muscle, Smooth / Q000502:physiology; D020239:Receptor Cross-Talk; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction
D000318:Adrenergic beta-Agonists; D018680:Cholinergic Antagonists; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic