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 A2 (TXA2) and the prostaglandins (PGs) in the pathogenesis and pathophysiology of asthma have fostered a wealth of studies but remain controversial. TXA2 and the bronchoconstrictor PGs, PGD2 and PGF2 alpha, are generated in greater amounts in asthmatic than in normal subjects. TXA2 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 hyperresponsiveness, a typical feature of asthma. Strategies for inhibition of TXA2 effects include antagonism of the TXA2 receptor (TP receptor) and inhibition of the thromboxane synthase. TP receptor antagonists could block the effects of all the bronchoconstrictor prostanoids because TXA2 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 TXA2 and broncho-constrictor PGs in the pathophysiology of asthma.
Devillier
P
P
Laboratoire de Pharmacologie, CHRU Grenoble, France.
Bessard
G
G
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000209:etiology; D002986:Clinical Trials as Topic; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013930:Thromboxane-A Synthase