Effects of C5a on guinea pig lung: Histamine release and mechanism of contraction

C5a, a product of complement system activation, causes a significant contraction of the isolated guinea pig trachea, and the antihlstamine diphenhydramine does not altter the rate, amplitude, or duration of the contraction (Regal et al., 1980). The present study demonstrates that over the ronge of C5a concentrations investigated, the C5a-induced contractile response of the trachea maximized, whereas the contraction of lung parenchymal strips and the release of histamine from chopped lung did not. In addition, the antihistamines, diphenhydramine and pyrilamine, caused a significant delay in the onset of the C5a-Induced contraction of lung parenchymal strips. When parenchymal strips from nonperfused lung were used, the maximum of the contraction was also reduced by pyrltamine. Aspirin and indomethacin effectively inhibited the C5a-induced contraction of tuns parenchymal strips, and Inhibition by a combination of aspirin and pyrilarnine was the mm of the inhibition by aspirin and the Inhibit ton by pyrilamine. The SRS-A antagonist, FPL 55712, caused a more rapid retaxation of the C5a-induced response over control. These studies suggest that products of the cyclo-oxygenase pathway are mediators involved in the C5a-Induced contraction of lung parenchyma, with histamine and leukotrienes contributing as well.