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 incr ements of thromboxane (TX) A2 level in both the plasma and bronchoalve olar lavage fluid. DP-1904 given orally relieved the bronchoconstricti on and increase in TXA2 in a dose-dependent manner. In platelet-deplet ed animals, antigen-induced bronchoconstriction and TXA2 release in th e 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 exclu ding platelets. In the platelet-deprived animal, DP-1904 showed furthe r significant inhibition of the constriction and plasma TXA2 level, an d 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 bronchoco nstriction, and endogenously originated from various cells including p latelets in guinea pigs. (C) 1998 The Italian Pharmacological Society.