Inhibitory effect of thromboxane A2 synthetase inhibitor, DP-1904, on antigen-induced contraction of human lung parenchyma.

Abstract

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.

OBJECTIVES:

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.

• Authors: C Fukushima, T Shimoda, H Matsuse, A Takao, H Sakai, S Asai, S Kohno, K Hara
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 77 Issue 6 Pg. 483-7 (Dec 1996) ISSN: 1081-1206 [Print] United States
• PMID: 8970439 (Publication Type: Journal Article)

Chemical References

• Antigens
• Enzyme Inhibitors
• Imidazoles
• Leukotrienes
• Tetrahydronaphthalenes
• Thromboxane B2
• nafagrel
• Thromboxane-A Synthase

Topics

• Aged
• Animals
• Antigens (pharmacology)
• Bronchoconstriction (drug effects, immunology)
• Dose-Response Relationship, Immunologic
• Enzyme Inhibitors (pharmacology)
• Female
• Humans
• Imidazoles (pharmacology)
• Leukotrienes (metabolism)
• Lung (metabolism, physiology)
• Male
• Middle Aged
• Mites (immunology)
• Muscle Contraction (drug effects, immunology)
• Tetrahydronaphthalenes (pharmacology)
• Thromboxane B2 (metabolism)
• Thromboxane-A Synthase (antagonists & inhibitors)