sta-2 and Hypersensitivity

Membrane-derived lipid mediators have been considered to play a major role in pathogenesis of bronchial asthma. However, the importance of and the interactions among each mediator are still unclear. We examined the role of thromboxane A2 (TXA2) and platelet-activating factor (PAF) in immediate asthmatic response (IAR) and interactions between these lipid mediators in guinea pig airway in vivo using a specific TXA2 antagonist S-1452 and a specific PAF antagonist Y-24180. We confirmed the activity of each antagonist, as S-1452 and Y-24180 significantly and dose-dependently inhibited bronchoconstriction induced by respective agonist inhalation. S-1452 inhibited IAR but Y-24180 did not, indicating that TXA2 plays a major role in IAR but PAF does not. S-1452 significantly inhibited PAF-induced bronchoconstriction but Y-24180 did not inhibit synthesized TXA2 (STA2)-induced bronchoconstriction, showing that the bronchoconstrictive effect of PAF is at least in part dependent on secondarily released TXA2, but TXA2 does not induce PAF production.

Topics: Administration, Inhalation; Animals; Antigens; Asthma; Azepines; Bridged Bicyclo Compounds; Bronchoconstriction; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Guinea Pigs; Hypersensitivity; Male; Platelet Activating Factor; Receptors, Prostaglandin; Thromboxane A2; Triazoles