Beta-adrenoceptors on smooth muscle, nerves and inflammatory cells.
Although the bronchodilator action of beta 2-adrenoceptor agonists in asthma is largely due to relaxation of airway smooth muscle, these agents have other effects which may contribute to their anti-asthma action. Human airway smooth muscle contains only beta 2-receptors which, when stimulated, stimulate a rise in intracellular cAMP and activation of PKA (protein kinase A), which in turn phosphorylates several cellular proteins, resulting in relaxation. However, beta-agonists also influence membrane K+ channels and induce smooth muscle relaxation without a rise in cAMP, and this mechanism appears to be the major feature of bronchodilatation in asthma. There is also evidence that beta-agonists may modulate neurotransmission in airways via prejunctional receptors on airway nerves, both sensory and motor. Blockade of prejunctional beta 2-receptors in asthma patients may lead to marked rise in acetylcholine release, with severe bronchoconstriction. Although beta-agonists have little or no effect on the chronic inflammatory response which underlies chronic airway hyper-responsiveness, they do inhibit the release of histamine from mast cells in vitro. The presence of beta-receptors has also been detected not only on mast cells but also on eosinophils, macrophages, lymphocytes and neutrophils, but beta-agonists have little or no inhibitory action on the activities of all these cells due to rapid tachyphylaxis.
Department of Thoracic Medicine, National Heart and Lung Institute, London, England.
P J
PJ
Barnes
D000818:Animals; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009130:Muscle, Smooth / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology*
D011943:Receptors, Adrenergic, beta