A review on leukotrienes and their receptors with reference to asthma.

Leukotrienes (LTs) including cysteinyl leukotrienes (CysLTs) and LTB4 are the most potent inflammatory lipid mediators and play a central role in the pathophysiology of asthma and other inflammatory diseases. These biological molecules mediate a plethora of contractile and inflammatory responses through specific interaction with distinct G protein-coupled receptors (GPCRs). The main objective of this review is to present an overview of the biological effects of CysLTs and their receptors, along with the current knowledge of mechanisms and role of LTs in the pathogenesis of asthma. CysLTs including LTC4, LTD4 and LTE4 are ligands for CysLT1 and CysLT2 receptors, and LTB4 is the agonist for BLT1 and BLT2 receptors. The role of CysLT1 receptor is well established, and most of the pathophysiological effects of CysLTs in asthma are mediated by CysLT1 receptor. Several CysLT1 antagonists have been developed to date and are currently in clinical practice. Most common among them are classical CysLT1 receptor antagonists such as montelukast, zafirlukast, pranlukast, pobilukast, iralukast, cinalukast and MK571. The pharmacological role of CysLT2 receptor, however, is less defined and there is no specific antagonist available so far. The recent demonstration that mice lacking both known CysLT receptors exhibit full/augmented response to CysLT points to the existence of additional subtypes of CysLT receptors. LTB4, on the other hand, is another potent inflammatory leukotriene, which acts as a strong chemoattractant for neutrophils, but weaker for eosinophils. LTB4 is known to play an important role in the development of airway hyper-responsiveness in severe asthma. However there is no LTB4 antagonist available in clinic to date. This review gives a recent update on the LTs including their biosynthesis, biological effects and the role of anti-LTs in the treatment of asthma. It also discusses about the possible existence of additional subtypes of CysLT receptors.