C5a-induced tracheal contraction: Effect of an SRS-A antagonist and inhibitors of arachidonate metabolism

C5a, a peptide derived from the fifth component of complement, has been shown to cause significant prolonged smooth muscle contraction in isolated guinea pig trachea. This contraction was not affected by the antihistamine diphenhydramine. To assess further the potential role that C5a may play in allergic bronchospasm, we investigated the role of products of arachidonate metabolism in the C5a-induced tracheal contraction. 5,8,11,14-Eicosatetraynoic acid, an inhibitor of lipoxygenase and cyclooxygenase, virtually eliminated the tracheal contraction induced by C5a. The prostaglandin synthesis inhibitor, acetylsalicylate, did not inhibit the C5a-induced tracheal contraction and enhanced the traceal response to acetylcholine. FPL 55712, an antagonist of slow reacting substance of anaphylaxis (SRS-A), almost completely inhibited the tracheal response to C5a and at higher concentrations employed, FPL 55712 also inhibited the tracheal response to exogenous prostaglandin F₂α. These studies indicate that C5a-induced tracheal contraction is mediated by a product or products of arachidonate metabolism, and is, at least in part, mediated by SRS-A.