INHIBITORY EFFECT OF THROMBOXANE A(2) SYNTHETASE INHIBITOR, DP-1904, ON ANTIGEN-INDUCED CONTRACTION OF HUMAN LUNG PARENCHYMA

Background: Several mediators are released from mast cells during alle rgic reactions. These substances cause contraction of airway smooth mu scles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A(2) (TXA(2)) has a part icularly strong bronchoconstrictive effect. Objectives: We examined an tigen-induced contraction of excised human lungs and the suppressive e ffects of TXA(2) synthetase inhibitor on TXA(2) release. Methods: Huma n lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus bath s, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA(2) synthetase, were added. Following the measurement of TXB(2) and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of T XB(2) and LT was measured after contraction. Results: Antigen-induced release of TXB(2) was significantly suppressed by DP-1904 in a concent ration-dependent manner. DP-1904 did not inhibit parenchymal contracti on and the release of LT. Conclusions: Antigen-induced parenchymal con traction was not suppressed by inhibition of TXA(2) release, suggestin g that DP-1904 may not be effective in asthma.