The fatty acid-derived mediators of inflammation include arachidonic acid (AA), its 5-, 12- and 15-lipoxygenase (LO) metabolites (e.g., leukotrienes (LTs), mono-hydroxyeicosatetraenoic acids (HETEs) and lipoxins) and its cyclooxygenase (prostaglandin (PG)H synthetase) metabolites PGD2, PGE2, PGF, PGI2 and thromboxane (Tx) A2. These molecules possess many activities in a variety of systems and have been implicated as critical mediators in the pathophysiology of several diseases including some of the pulmonary system. In particular, significant attention has focused on the potential pivotal role of the cysteinyl or peptido leukotrienes (CysLTs: LTC4, LTD4, LTE4) and LTB4 in a variety of inflammatory disorders, notably asthma [1-3], arthritis [3–5] and inflammatory bowel disease (IBD) [3, 6–8]. The LTs produce a variety of effects in the respiratory system including smooth muscle contraction, enhanced mucus secretion [9, 10], inflammatory cell infiltration [11–13] and activation [11, 14], increased microvascular permeability [11, 15–17] and interactions with neuronal inputs [18], which may contribute to the etiology of pulmonary disorders. This chapter will focus on the ability of the LTs to contract airways smooth muscle and the signal transduction mechanisms and receptors involved in this action. In addition, the strategies pursued in the identification and development of drugs to control the release and effects of the LTs will be discussed, including a summary of the highlights of preclinical and clinical studies with representative compounds.


Airway Smooth Muscle Allergy Clin Immunol Airway Smooth Muscle Contraction Airway Smooth Muscle Contractility LTD4 Receptor Antagonist 
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Copyright information

© Birkhäuser Verlag Basel/Switzerland 1995

Authors and Affiliations

  • Douglas W. P. Hay
    • 1
  • David Raeburn
    • 2
  1. 1.Department of Pulmonary PharmacologySmithKline Beecham PharmaceuticalsKing of PrussiaUSA
  2. 2.Department of InflammationRhône-Poulenc Rorer, Inc.CollegevilleUSA

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