Open AccessIn Vitro Pharmacology of a Novel Non-Peptide Angiotensin II-Receptor Antagonist, E4177
Author(s) -
Hideki Okunishi,
Keifu Song,
Yuko Oka,
Takatoshi Kobayashi,
Tatsuhiko Kawamoto,
Hiroki Ishihara,
Nobuhito Mori,
Mizuo Miyazaki
Publication year - 1993
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.62.351
Subject(s) - pharmacology , antagonist , angiotensin ii , in vitro , chemistry , receptor antagonist , peptide , receptor , medicine , biochemistry
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.