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Clinical Reviews in Allergy & Immunology

, Volume 17, Issue 1–2, pp 179–191 | Cite as

Leukotriene receptors

  • Sven-Erik Dahlén
Basic Sciences The Immunobiology of Leukotriene Inhibitors

Conclusions

TheCysLT1-antagonists are currently as a class being introduced as new therapy for asthma and perhaps in the future also as treatment for other inflammatory disorders. These achievements have been made by the application of classical strategies, such as organic synthesis of new chemical entities, pharmacology screening in smooth muscle bioassays, and subsequent clinical testing in healthy subjects and patients with asthma.

In parallel, the further exploration of leukotriene effects and the application of currently available antagonist has established that certain effects of cysteinyl-LTs are resistant to inhibition by the present class of antagonists. This has led to the classification of such receptors asCysLT2. There is no selectiveCysLT2 antagonist available, but the structural analog of cysteinyl-LTs BAY u9773 has been shown to competitively antagonize cysteinyl-LTs at both theCysLT1 and theCysLT2 receptor. Further subclasses of theCysLT receptors are, however, to be expected on the basis of, for example, quite remarkable differences in sensitivity to agonists and antagonists between tissues, even in the same species. Although most effects of cysteinyl-LTs that may be involved in the pathogenesis of asthma are believed to be susceptible toCysLT1-antagonism, in humans it is only the bronchoconstrictive effect of LTD4 that unequivocally has been demonstrated to be inhibited byCysLT1-antagonists. A complete understanding of the role of cysteinyl-LTs in asthma will necessitate not only the molecular characterization of the receptors but also the development of selective agonists and antagonists at different receptor subclasses. This would also help the definition of the role of cysteinyl-LTs in other pulmonary and extra-pulmonary diseases, as well as physiological responses.

Keywords

Clinical Review Airway Smooth Muscle LTB4 Immunology Volume Human Bronchus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Humana Press Inc 1999

Authors and Affiliations

  1. 1.Experimental Asthma and Allergy Research, The National Institute of Environmental MedicineKarolinska InstitutetStockholmSweden

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