e-6123 and ebastine

We examined the role of a cytosolic phospholipase A2 (cPLA2) in antigen-induced eosinophil infiltration of airways and in airway hyperresponsiveness to methacholine. Inhibition of cPLA2, or blockade of the platelet-activating factor (PAF) receptor, blocked antigen-induced airway hyperresponsiveness and suppressed eosinophil infiltration. Neither cyclooxygenase nor 5-lipoxygenase inhibition had either effect. We show here that, in antigen-sensitized guinea pigs, cPLA2 inhibition prevents both eosinophilic infiltration and subsequent airway hyperresponsiveness after antigen challenge. We also show that this effect is mediated by first-step hydrolysis of membrane phospholipid into lysophospholipid rather than by prostanoid or leukotriene metabolites of arachidonate.

Topics: Animals; Antigens; Azepines; Benzoquinones; Bronchoconstriction; Butyrophenones; Eicosapentaenoic Acid; Enzyme Inhibitors; Eosinophils; Guinea Pigs; Indomethacin; Male; Methacholine Chloride; Phospholipases A; Phospholipases A2; Piperidines; Respiratory Hypersensitivity; Triazoles