The role of cyclic AMP in the inhibition of leukotriene biosynthesis by neuropeptides.

Certain neuropeptides, including vasoactive intestinal peptide, inhibit peptidoleukotriene release from platelet activating factor-stimulated rat lung. We have now shown that vasoactive intestinal peptide will also inhibit peptidoleukotriene release from platelet activating factor-stimulated or ovalbumin-challenged guinea pig lung, but not from calcium ionophore-stimulated rat or guinea pig lung. In rat lung a pre-incubation with the peptide prior to addition of platelet activating factor was required for the effect to be maximal. When vasoactive intestinal peptide was substituted with cyclic AMP, the inhibitory effect was reproduced. In addition, pre-incubation with MDL 12330A, an inhibitor of adenylate cyclase, reduced the inhibitory effect of vasoactive intestinal peptide on platelet activating factor-stimulated leukotriene C4 biosynthesis. We suggest that the inhibition of platelet activating factor-stimulated peptidoleukotriene release in rat lung by vasoactive intestinal peptide involves the events prior to phospholipase A2 activation and requires cyclic AMP as a mediator.