Cysteinyl leukotrienes and their receptors: molecular and functional characteristics - PubMed (original) (raw)

Review

doi: 10.1159/000312669. Epub 2010 Jun 2.

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Review

Cysteinyl leukotrienes and their receptors: molecular and functional characteristics

R K Singh et al. Pharmacology. 2010.

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Abstract

The cysteinyl leukotrienes (CysLTs) are a family of potent inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells including mast cells, eosinophils, basophils and macrophages. The family includes leukotriene C(4) (LTC(4)), leukotriene D(4) (LTD(4)) and leukotriene E(4) (LTE(4)), which are potent biological mediators in the pathophysiology of inflammatory diseases and trigger contractile and inflammatory processes through the specific interaction with cell surface receptors, belonging to the superfamily of G-protein-coupled receptor. Pharmacological characterizations have suggested the existence of at least 2 types of CysLT receptors based on potency of agonist and antagonist, designated as CysLT(1) and CysLT(2). The CysLT(1) receptors are mostly expressed in lung smooth muscle cells, interstitial lung macrophages and the spleen, and it has been studied a lot elucidating its role in the etiology of airway inflammation and asthma. On the other hand, CysLT(2) receptors are present in the heart, brain and adrenal glands. This review discusses the role of CysLTs and their receptor in the pathophysiology of various inflammatory disorders. The understanding of CysLTs and their receptors in allergic airway disease is currently limited to CysLT(1)-receptor-mediated effects, and the role of the CysLT(2) receptors is pharmacologically less well defined, as there is no specific antagonist available yet. Specific CysLT(2)-receptor-selective antagonists would be very helpful to identify the precise role of CysLT and their receptors. Some recent evidence indicates the existence of additional receptor subtypes and requires further investigation for a better understanding of the role of the CysLT receptors. This review is an effort to summarize the localization, regulation and expression pattern along with the molecular and functional pharmacology of the CysLT receptors and to discuss their role in the pathophysiology of different diseases along with the recent update.

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