Inhibitory effect of thromboxane A2 synthetase inhibitor, DP-1904, on antigen-induced contraction of human lung parenchyma.
BACKGROUND
Several mediators are released from mast cells during allergic reactions. These substances cause contraction of airway smooth muscles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A2 (TXA2) has a particularly strong bronchoconstrictive effect.


OBJECTIVE
We examined antigen-induced contraction of excised human lungs and the suppressive effects of TXA2 synthetase inhibitor on TXA2 release.


METHODS
Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus baths, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA2 synthetase, were added. Following the measurement of TXB2 and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of TXB2 and LT was measured after contraction.


RESULTS
Antigen-induced release of TXB2 was significantly suppressed by DP-1904 in a concentration-dependent manner. DP-1904 did not inhibit parenchymal contraction and the release of LT.


CONCLUSIONS
Antigen-induced parenchymal contraction was not suppressed by inhibition of TXA2 release, suggesting that DP-1904 may not be effective in asthma.
Fukushima
C
C
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Shimoda
T
T
Matsuse
H
H
Takao
A
A
Sakai
H
H
Asai
S
S
Kohno
S
S
Hara
K
K
D000368:Aged; D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000941:Antigens; D004791:Enzyme Inhibitors; D007093:Imidazoles; D015289:Leukotrienes; D013764:Tetrahydronaphthalenes; D013929:Thromboxane B2; C056295:nafagrel; D013930:Thromboxane-A Synthase