Characterization of the human cysteinyl leukotriene CysLT(1) receptor

The cysteinyl leukotrienes-leukotriene C-4(LTC4), leukotriene D-4(LTD4) and leukotriene E-4(LTE4)-are important mediators of human bronchial asthma(1- 3). Pharmacological studies have determined that cysteinyl leukotrienes act ivate at least two receptors, designated CysLT(1) and CysLT(2) (refs 4-6). The CysLT(1)-selective antagonists, such as montelukast (Singulair)(7-10), zafirlukast (Accolate)(11) and pranlukast (Onon)(12), are important in the treatment of asthma. Previous biochemical characterization of CysLT(1) anta gonists and the CysLT(1) receptor has been in membrane preparations from ti ssues enriched for this receptor(13). Here we report the molecular and phar macological characterization of the cloned human CysLT(1) receptor. We desc ribe the functional activation (calcium mobilization) of this receptor by L TD4 and LTC4, and competition for radiolabelled LTD4 binding to this recept or by the cysteinyl leukotrienes and three structurally distinct classes of CysLT(1)-receptor antagonists. We detected CysLT(1)-receptor messenger RNA in spleen, peripheral blood leukocytes and lung. In normal human lung, exp ression of the CysLT(1)-receptor mRNA was confined to smooth muscle cells a nd tissue macrophages. Finally, we mapped the human CysLT(1)-receptor gene to the X chromosome.