Platelet-activating factor-induced contraction of guinea-pig lung parenchymal strips: possible involvement of arachidonate metabolites.

The identification of the mediators possibly involved in platelet-activating factor (PAF)-induced contraction of guinea-pig lung parenchymal strips (GPLP) was attempted by means of antagonists and inhibitors. Histamine, serotonin, acetylcholine (ACh) or other transmitters released from the nerve terminals are not likely to play a role in this response, since specific antagonists and tetrodotoxin did not affect the contraction. PAF antagonists (brotizolam and WEB 2086) produced a concentration-dependent inhibition of the contraction. Inhibitors of TXA2 synthesis (dazoxiben) and of 5-lipoxygenase (nordihydroguaiaretic acid and AA 861) and antagonists of TXA2 (ICI 159995) and peptidoleukotrienes (L 649923 and LY 171883, but not FPL 55712) produced a significant inhibition of the PAF-induced response at concentrations which did not reduce the ACh-induced response. These results suggest that arachidonate metabolites, both of the cyclo-oxygenase and of the lipoxygenase pathway, are determinants of the PAF-induced contraction of GPLP.