Endothelin receptor distribution and function in the airways

Abstract

1. Within the lung, endothelin (ET)-1 is synthesized and released by airway epithelial and vascular endothelial cells, as well as by inflammatory cells, such as macrophages. Following release, ET-1 can modulate the activities of a wide range of different cell types within the lung through the stimulation of specific endothelin ETA and ETB receptors. The present review focuses on recent advances in our understanding of the distribution and function of endothelin receptors within the airway wall and peripheral lung and, where possible, particular attention is given to studies using human cells, tissues and subjects. 2. The highest densities of endothelin receptors within the lung appear to be associated with airway smooth muscle and the alveolar septae. The relative proportions of ETA and ETB receptors present within these tissues display marked interspecies differences, although ETB receptors predominate at both sites in human lung. 3. The effects induced by ET-1 within the lung include contraction and proliferation of airway smooth muscle, facilitation of cholinergic neurotransmission, mucous gland hypersecretion, microvascular leakage and inflammatory cell influx and activation. There is also evidence that a proportion of ETB receptors in the pulmonary microvasculature act as clearance receptors for endothelin-1. 4. Evidence to date suggests that changes in the endothelin content within the airway wall, conceivably associated with lung pathology, are likely to have profound effects on the function of many cells within the lung.