Endothelins and airways--a short review.

Endothelins (ETs) are a multifunctional large family of polypeptides. There are three well recognized members in this family (ET-1, ET-2, and ET-3) of which ET-1 appears to be the most important. They have been shown to play an important role in the pathogenesis of many life threatening diseases of humans and animals. They also perform a wide variety of physiological roles. The most important property of ETs is smooth muscle contraction, which allows them to play an important role in the pathogenesis of many vascular, gastrointestinal, urogenital and airway diseases. Another important feature of ETs is their influence on the immune system. Many animal and human studies have shown that antagonists of ET receptors can remarkably alleviate many disease symptoms. ETs produce their effect by acting via two established types of receptors namely ET-A and ET-B, which are present in various type of cells in the body. These receptors have varied and sometimes opposite functions. Pulmonary vascular endothelium is the richest source of ET in the body. Lung is the primary organ of ET metabolism and clearance. It has been reported that ETs play a pivotal role in the pathogenesis of asthma, chronic obstructive pulmonary disease, bronchiolitis obliterans and other important airway diseases. Many of these obstructive airway diseases are characterized by bronchoconstriction, mucous hyperplasia, airway remodeling and inflammation. ET is involved in all of these symptoms. In spite of its involvement in many diseases, the exact role of ET in the pathogenesis of these diseases remains unclear. The purpose of this review is to give the reader an insight regarding the importance of multitude and diverse roles played by ETs in various airway diseases.