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Lynch, K.R. et al.

Characterization of the human cysteinyl leukotriene CysLT1 receptor.

The cysteinyl leukotrienes-leukotriene C4(LTC4), leukotriene D4(LTD4) and leukotriene E4(LTE4)-are important mediators of human bronchial asthma. Pharmacological studies have determined that cysteinyl leukotrienes activate at least two receptors, designated CysLT1 and CysLT2. The CysLT1-selective antagonists, such as montelukast (Singulair), zafirlukast (Accolate) and pranlukast (Onon), are important in the treatment of asthma. Previous biochemical characterization of CysLT1 antagonists and the CysLT1 receptor has been in membrane preparations from tissues enriched for this receptor. Here we report the molecular and pharmacological characterization of the cloned human CysLT1 receptor. We describe the functional activation (calcium mobilization) of this receptor by LTD4 and LTC4, and competition for radiolabelled LTD4 binding to this receptor by the cysteinyl leukotrienes and three structurally distinct classes of CysLT1-receptor antagonists. We detected CysLT1-receptor messenger RNA in spleen, peripheral blood leukocytes and lung. In normal human lung, expression of the CysLT1-receptor mRNA was confined to smooth muscle cells and tissue macrophages. Finally, we mapped the human CysLT1-receptor gene to the X chromosome.[1]

References

Characterization of the human cysteinyl leukotriene CysLT1 receptor. Lynch, K.R., O'Neill, G.P., Liu, Q., Im, D.S., Sawyer, N., Metters, K.M., Coulombe, N., Abramovitz, M., Figueroa, D.J., Zeng, Z., Connolly, B.M., Bai, C., Austin, C.P., Chateauneuf, A., Stocco, R., Greig, G.M., Kargman, S., Hooks, S.B., Hosfield, E., Williams, D.L., Ford-Hutchinson, A.W., Caskey, C.T., Evans, J.F. Nature (1999) [Pubmed]

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