Effect of VIP, phenoxybenzamine and prednisolone on cyclic nucleotide content of isolated guinea-pig lung and trachea.

Vasoactive intestinal polypeptide (VIP) increased the cyclic AMP content of guinea pig lung and tracheal tissues. Combinations of the peptide with prednisolone or with phenoxybenzamine potentiated the effect of VIP on cyclic AMP. The trachea-relaxant effect of VIP also was reinforced by the addition of prednisolone or phenoxybenzamine. At the same time, cyclic GMP content in these tissues changed little in response to these agents. The results provide a biochemical basis for the tracheal-relaxant action of these agents, and for the potentiation of bronchodilation by prednisolone and by alpha-receptor blockade. The findings are also consistent with the view that relaxation of airway smooth muscle is mediated by an elevation of intracellular cyclic AMP.