Cysteinyl leukotriene receptors

Abstract

The cysteinyl leukotrienes, leukotriene C 4 (LTC 4), leukotriene D 4 (LTD 4) and leukotriene E 4 (LTE 4), activate contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. Pharmacological characterizations identified at least two subtypes of cysteinyl leukotriene (CysLT) receptor based on agonist and antagonist potency for biological responses. The rank potency of agonist activation for the CysLT 1 receptor is LTD 4>LTC 4>LTE 4 and for the CysLT 2 receptor is LTC 4=LTD 4>LTE 4. CysLT 1 selective receptor antagonists are efficacious in the treatment of asthma. No selective CysLT 2 receptor antagonists have been described. Molecular identification of the human and mouse CysLT 1 and CysLT 2 receptors has confirmed their structure as putative seven transmembrane domain G protein-coupled receptors and largely confirmed the previous pharmacological characterizations. The CysLT 1 receptor is most highly expressed in spleen, peripheral blood leukocytes including eosinophils, and lung smooth muscle cells and interstitial lung macrophages. The CysLT 2 receptor is most highly expressed in the heart, adrenal medulla, placenta and peripheral blood leukocytes. The molecular identification of the mouse CysLT 1 and CysLT 2 receptors show similar but not identical profiles to the orthologous human receptors.