Correlative alteration of thromboxane A2 with antigen-induced bronchoconstriction and the role of platelets as a source of TXA2 synthesis in guinea pigs: effect of DP-1904, an inhibitor of thromboxane synthetase.
A marked and sustained bronchoconstriction after antigen challenge was produced in actively sensitised guinea pigs, and correlated with increments of thromboxane (TX) A2 level in both the plasma and bronchoalveolar lavage fluid. DP-1904 given orally relieved the bronchoconstriction and increase in TXA2 in a dose-dependent manner. In platelet-depleted animals, antigen-induced bronchoconstriction and TXA2 release in the plasma were significantly reduced compared to those of non-platelet-depleted animals, indicating that platelets are a major cell source of TXA2 production, the remainder originating from the other cells excluding platelets. In the platelet-deprived animal, DP-1904 showed further significant inhibition of the constriction and plasma TXA2 level, and therefore likely inhibits TXA2 synthesis of various cells, including platelets, in the bloodstream. The results suggested that TXA2 is an important mediator responsible for producing antigen-induced bronchoconstriction, and endogenously originated from various cells including platelets in guinea pigs.
Takami
M
M
Department of Medical Information, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.
Tsukada
W
W
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000941:Antigens; D001249:Asthma / Q000097:blood* / Q000139:chemically induced; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000097:blood*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D018927:Anti-Asthmatic Agents; D000941:Antigens; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013764:Tetrahydronaphthalenes; D013929:Thromboxane B2; D013928:Thromboxane A2; C056295:nafagrel; D013930:Thromboxane-A Synthase