VASOACTIVE-INTESTINAL-PEPTIDE AND HELODERMIN INHIBIT THE RELEASE OF CYCLOOXYGENASE PRODUCTS INDUCED BY LEUKOTRIENE-D(4) AND BRADYKININ FROM GUINEA-PIG PERFUSED LUNG

Vasoactive intestinal peptide (VIP, 10 nM) inhibited the release of cyclo-oxygenase products, detected by both bioassay and radioimmunoassay, induced by leukotriene (LT) D4 (3-30 pmol) and bradykinin (BK, 3-30 nmol) from guinea-pig isolated perfused lung. Helodermin (10 nM), a peptide that is structurally related to VIP. and salbutamol (10 nM), a beta-2-adrenoceptor agonist, evoked a similar inhibitory effect on LTD4-induced release of cyclo-oxygenase products. Thc generation of TxB2 and 6-keto-PGF1-alpha following stimulation with exogenously administered arachidonic acid (30-300 nmol) was not significantly attenuated in the presence of either VIP, helodermin or salbutamol. These results show that VIP, helodermin and salbutamol are potent inhibitors of the release of cyclo-oxygenase products induced by agonists known to activate endogenous arachidonic acid metabolism in guinea-pig lung. Since the metabolism of exogenously administered arachidonic acid was not inhibited these results suggest that the inhibitory effect may be exerted on events preceding the mobilisation of arachidonic acid and may involve cyclic AMP.