Relaxant effect of pituitary adenylate cyclase-activating polypeptide on guinea-pig tracheal smooth muscle

Abstract We investigated the relaxant effect of the pituitary adenylate cyclase-activating polypeptide with 27 residues (PACAP27) and with 38 residues (PACAP38) on guinea-pig tracheal smooth muscle. Both forms of PACAP showed dose-dependent relaxant effects. The EC 50 of PACAP27 was 8.7 ± 1.9 × 10 -8 M and that of PACAP38 was 6.8 ± 1.0 × 10 -8 M. Both increased cyclic AMP levels dose dependently and the elevation of cyclic AMP preceded the relaxation of tracheal smooth muscle. There was a marked difference in the duration of action of the two peptides. PACAP38 showed a longer-lasting relaxation compared to PACAP27. Furthermore PACAP38 maintained significantly higher levels of cyclic AMP, with cyclic AMP levels at 60 min after a 5-min exposure to PACAPs (10 -6 M) being 14.0±1.4 pM/mg protein for PACAP27 and 35.9±2.4 pM/mg protein for PACAP38. These results suggest that PACAP27 and PACAP38 may be novel potent relaxants in tracheal smooth muscle and their relaxant effect might be mediated by cyclic AMP. However PACAP38 had a longer-lasting action on relaxation of tracheal smooth muscle and production of tissue cyclic AMP than PACAP27.