BETA-2 ADRENERGIC-RECEPTORS IN ASTHMA - A CURRENT PERSPECTIVE

The role of the beta(2)-adrenergic receptor in both the pathogenesis and treatment of asthma has been a subject of intense speculation and investigation for 25 years. The physiological effects of endogenous circulating catecholamines and exogenous adrenergic agonists in the lung are mediated by the beta(2)-adrenergic receptor, which is present on a variety of cell types. Documented effects of beta(2)-adrenergic receptor activation in the human lung include smooth muscle relaxation, inhibition of acetylcholine release from cholinergic nerve terminals, stimulation of serous and mucous cell secretion, increases in ciliary beat frequency, promotion of water movement into the airway lumen by stimulation of ion secretion across the apical membrane of epithelial cells, increase in bronchial blood flow, reduction in venular permeability, and inhibition of mediator release from some, but not all, inflammatory cells. Beta(2)-adrenergic receptors are present in normal or increased numbers on asthmatic airway smooth muscle but are uncoupled in severe asthma, leading to functional hyporesponsiveness, probably due to the effects of inflammatory mediators. There is also evidence for dysfunction of beta(2)-adrenergic receptors on circulating inflammatory cells following mediator release. However, dysfunction of the receptors on airway smooth muscle and inflammatory cells is unlikely to be of primary importance in the pathogenesis of asthma. There is increasing concern that regular beta(2)-adrenergic receptor agonist use in the therapy of asthma is deleterious. Although a number of theories have been advanced to explain such an effect, none is well established and further research is urgently required.