Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part I: synthesis, receptors and role of leukotrienes in asthma

Abstract

Asthma is a chronic inflammatory disease associated with airflow obstruction. Airflow obstruction results from contraction of airway smooth muscle, mucosal oedema, increased secretion of mucus and infiltration of the airway wall by inflammatory cells, particularly eosinophils. Leukotrienes are thought to contribute to the pathophysiology of asthma. Leukotrienes are synthesised from arachidonic acid by a specific synthesis pathway whose key enzyme is 5-lipoxygenase. Cysteinyl leukotrienes (leukotrienes C4, D4 and E4) have been shown to mimic all the pathologic changes that are characteristic of asthma, whereas leukotriene B4 does not appear to exert biological properties relevant to asthma. Cysteinyl leukotrienes bind to two receptor subtypes: CysLT1 and CysLT2. Most of the biological properties of cysteinyl leukotrienes relevant to asthma are mediated through CysLT1 receptor stimulation.