Important role of peptide leukotrienes (p-LTs) in the resting tonus of isolated human bronchi.
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. (E)-2,2-Diethyl-3'-[2-[2-(4-isopropyl)-thiazoyl]ethenyl]succina nilic 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.
Kohno
S
S
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Tsuzuike
N
N
Yamamura
H
H
Nabe
T
T
Horiba
M
M
Ohata
K
K
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000096:biosynthesis / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011863:Radioimmunoassay; D013844:Thiazoles / Q000494:pharmacology
D016227:Benzoquinones; D007202:Indicators and Reagents; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; C077265:MCI 826; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D007213:Indomethacin