Thromboxane A2 and related prostaglandins in airways

Asthma is now thought to be a chronic inflammatory disease of the airways. The roles of prostanoids, thromboxane A 2 (TXA 2 ) and the prostaglandins (PGs) in the pathogenesis and pathophysiology of asthma have fostered a wealth of studies but remain controversial. TXA 2 and the bronchoconstrictor PGs, PGD 2 and PGF 2α , are generated in greater amounts in asthmatic than in normal subjects. TXA 2 is a potent constrictor of airway smooth muscle, an inducer of acetylcholine release and of airway microvascular leakage. It may participate in the thickening and the remodeling of the airway wall which may contribute to the airway hyperresponsive-ness, a typical feature of asthma. Strategies for inhibition of TXA 2 effects include antagonism of the TXA 2 receptor (TP receptor) and inhibition of the thromboxane synthase. TP receptor antagonists could block the effects of all the bronchoconstrictor prostanoids because TXA 2 as well as the bronchoconstrictor PGs act through activation of lung TP receptor. The recent development of specific and potent TP receptor antagonists and inhibitors of thromboxane synthase has provided tools to assess the role of TXA 2 and bronchoconstrictor PGs in the pathophysiology of asthma.