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Distribution of Receptor Targets in the Lung

Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom

Correspondence and requests for reprints should be addressed to Professor P. J. Barnes, Ph.D., Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK. E-mail: p.j.barnes{at}imperial.ac.uk

Most of the drugs that are currently used to treat airway diseases interact with receptors expressed by cells in the airways. This makes inhaled delivery efficient because it reaches the key target cells and has a low risk of systemic side effects. Both ß₂-agonists and anticholinergics target autonomic receptors on airway smooth muscle of large and small airways. Inhaled ß₂-agonists also interact with ß₂-receptors expressed on other important target cells, including mast cells and postcapillary venules. Anticholinergic bronchodilators target M₃ muscarinic receptors on airway smooth muscle, which in small airways may be activated by extraneuronal acetylcholine. Corticosteroids target glucocorticoid receptors (GR), which are widely distributed so that they are best given by inhalation to interact with intracellular GR in the respiratory tract and to avoid side effects from activation of GR in extrapulmonary tissues such as bone. By contrast, cysteinyl-leukotriene 1 receptors are mainly expresses in airway smooth muscle so that antileukotrienes are less effective clinically than ß₂-agonists and corticosteroids, but oral delivery is possible as there are minimal side effects. There are many other receptor targets in lung and for several of these receptors, such as receptors for chemotactic agonists, selective antagonists are in clinical development. For drugs that inhibit chemotactic receptors, systemic delivery is more appropriate to prevent the inflammatory cells that bear these receptors from being recruited into the airways by locally released chemotactic factors. Many novel receptors, including orphan receptors, have now been identified as these may be future targets for developing novel therapies for asthma and chronic obstructive pulmonary disease.

Key Words: ß₂-adrenoceptor • chemokine receptor • cysteinyl-leukotriene receptor • glucocorticoid receptor • muscarinic receptor

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