Inhibitory effect of a peptide leukotriene antagonist ONO-1078 on LTD4- and antigen-induced thromboxane B2 production in guinea pig lungs.
The effect of a peptide leukotriene receptor antagonist ONO-1078 on the production of thromboxane (Tx) B2 induced by leukotriene (LT) D4 and antigen challenge was examined in guinea pig lungs. LTD4 (1-1,000 nM) induced a concentration-dependent production of TxB2 in non-sensitized guinea pig lungs and ovalbumin challenge (0.01-100 micrograms/ml) produced TxB2 and peptide leukotrienes in a concentration-dependent manner in ovalbumin-sensitized guinea pig lungs. ONO-1078 inhibited LTD4 (100 nM)-induced TxB2 production with the IC50 value of 0.24 microM. Furthermore, ONO-1078 inhibited antigen (10 micrograms/ml)-induced TxB2 production with the IC50 value of 0.14 microM without effect on the production of peptide leukotrienes. These results suggest that ONO-1078 may prevent the antigen-induced production of TxB2 through the blockade of the activation of receptors by endogenously generated peptide leukotrienes.
Obata
T
T
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Okada
Y
Y
Nakagawa
N
N
Terawaki
T
T
Aishita
H
H
D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001886:Bordetella pertussis; D002867:Chromones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000941:Antigens; D002867:Chromones; D008689:Methacrylates; D013189:SRS-A; D013929:Thromboxane B2; C006312:FPL 55712; D010047:Ovalbumin; D013930:Thromboxane-A Synthase; C034364:ozagrel; C047681:pranlukast; D007213:Indomethacin