Inhibitory Effects of OKY-046 on Spasmogen-Induced Bronchoconstrictions in Sensitized and Non-Sensitized Guinea Pigs

We examined the effect of thromboxane A2(TXA2) synthetase inhibitor, OKY-046, on bronchoconstriction induced by antigen and various spasmogenic mediators in guinea pigs in vivo. Further, inhibitory activities of OKY-046 on contractions of isolated tracheae and lung parenchymal strips induced by vari...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1990, Vol.52(2), pp.307-317
Main Authors: NAMBU, Fumio, MOTOISHI, Mariko, OMAWARI, Nagashige, OKEGAWA, Tadao, KAWASAKI, Akiyoshi, IKEDA, Shigeru
Format: Article
Language:English
Subjects:
Acrylates - pharmacology
Animals
Biological and medical sciences
Blood Pressure - drug effects
Bordetella pertussis - immunology
Bronchi - drug effects
Guinea Pigs
Histamine - pharmacology
Histamine and antagonists. Allergy
In Vitro Techniques
Indomethacin - pharmacology
Leukotrienes - pharmacology
Lung - drug effects
Male
Medical sciences
Methacrylates - pharmacology
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Pharmacology. Drug treatments
Platelet Activating Factor - pharmacology
Prostaglandin D2 - pharmacology
Thromboxane-A Synthase - antagonists & inhibitors
Trachea - drug effects
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Summary:We examined the effect of thromboxane A2(TXA2) synthetase inhibitor, OKY-046, on bronchoconstriction induced by antigen and various spasmogenic mediators in guinea pigs in vivo. Further, inhibitory activities of OKY-046 on contractions of isolated tracheae and lung parenchymal strips induced by various contractile agents were also investigated in vitro. OKY-046, but not indomethacin, significantly inhibited antigen-induced bronchoconstriction in a dose-dependent manner. Moreover, OKY-046 attenuated bronchoconstrictions induced by peptide leukotrienes (LTs) and platelet activating factor (PAF), but not those by histamine, prostaglandin D2 (PGD2) and STA2 (a stable TXA2 mimetic agent). Although contractile responses induced by spasmogens such as peptide LTs, PAF and histamine were not influenced by OKY-046 in isolated tracheae, OKY-046 elicited significant and concentration-dependent inhibitions against contractile responses induced by peptide LTs and PAF in isolated lung parenchymal strips. These results suggest the possible involvement of TXA2 in the development of anaphylactic bronchoconstriction in sensitized guinea pigs.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.52.307