
To characterize the cysteinyl‐leukotriene receptors (CysLT receptors) in isolated human pulmonary arteries, ring preparations were contracted with leukotriene C4 (LTC4) and leukotriene D4 (LTD4) in either the absence or presence of the selective CysLT1 receptor antagonists, ICI 198615, MK 571 or the dual CysLT1/CysLT2 receptor antagonist, BAY u9773. Since the contractions induced by the cysteinyl‐leukotrienes (cysLTs) in intact preparations failed to attain a plateau response over the concentration range studied, the endothelium was removed and the tissue treated continuously with indomethacin (Rubbed+INDO). In these latter preparations, the pEC50 for LTC4 and LTD4 were not significantly different (7.61±0.07, n=20 and 7.96±0.09, n=22, respectively). However, the LTC4 and LTD4 contractions were markedly potentiated when compared with data from intact tissues. Leukotriene E4 (LTE4) did not contract human isolated pulmonary arterial preparations. In addition, treatment of preparations with LTE4 (1 μM; 30 min) did not modify either the LTC4 or LTD4 contractions. Treatment of preparations with the S‐conjugated glutathione (S‐hexyl‐GSH; 100 μM, 30 min), an inhibitor of the metabolism of LTC4 to LTD4, did not modify LTC4 contractions. The pEC50 values for LTC4 were significantly reduced by treatment of the preparations with either ICI 198615, MK 571 or BAY u9773 and the pKB values were: 7.20, 7.02 and 6.26, respectively. In contrast, these antagonists did not modify the LTD4 pEC50 values. These findings suggest the presence of two CysLT receptors on human pulmonary arterial vascular smooth muscle. A CysLT1 receptor with a low affinity for CysLT1 antagonists and a novel CysLT receptor subtype, both responsible for vasoconstriction. Activation of this latter receptor by LTC4 and LTD4 induced a contractile response which was resistant to the selective CysLT1 antagonists (ICI 198615 and MK 571) as well as the non‐selective (CysLT1/CysLT2) antagonist, BAY u9773. British Journal of Pharmacology (2002) 137, 1339–1345. doi:10.1038/sj.bjp.0704991
Male, Receptors, Leukotriene, Binding Sites, Dose-Response Relationship, Drug, Membrane Proteins, Muscle, Smooth, In Vitro Techniques, Middle Aged, Pulmonary Artery, Leukotriene C4, Leukotriene D4, Vasoconstriction, Humans, Leukotriene Antagonists, Female, Aged
Male, Receptors, Leukotriene, Binding Sites, Dose-Response Relationship, Drug, Membrane Proteins, Muscle, Smooth, In Vitro Techniques, Middle Aged, Pulmonary Artery, Leukotriene C4, Leukotriene D4, Vasoconstriction, Humans, Leukotriene Antagonists, Female, Aged
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