Important Role of Peptide Leukotrienes (p-LTs) in the Resting Tonus of Isolated Human Bronchi.

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The quality of the resting tonus in isolated human bronchi was investigated using a peptide leukotriene (p-LT) antagonist, a 5-lipoxygenase inhibitor and others. (<I>E</I>)-2, 2-Diethyl-3 [2-[2-(4-isopropyl)-thiazoyl]ethenyl]succinanilic acid sodium salt (MCI-826), a newly synthesized compound that is a highly selective antagonist to LTD4 and LTE4, markedly relaxed the isolated human bronchi at low concentrations. A selective and competitive arachidonate 5-lipoxygenase inhibitor, 2, 3, 5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1, 4-benzoquinone (AA-861), also potently lowered the tonus. In addition, a large amount of spontaneously formed p-LTs was detected in the isolated human bronchial tissue as well as the lung parenchymal tissue. The isolated human bronchi responded to indomethacin treatment with contractions and the acceleration of p-LT formation. Atropine, an anticholinergic; mepyramine, an antihistaminic; and OKY-046, a thromboxane synthetase inhibitor, all showed no effect on the resting tonus. Taking into consideration the high responsiveness of the human airway smooth muscle to p-LTs and the present results, which were different from those on isolated guinea pig tracheas, it is strongly suggested that the spontaneously formed p-LTs largely participate in the resting tonus of the majority of isolated human bronchi.
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