Inhibition of pituitary adenylate cyclase activating polypeptide induced relaxation of guinea-pig tracheal smooth muscle by charybdotoxin.

The aim of the present study was to investigate whether or not charybdotoxin (CAS 95751-30-7, ChTX), a selective and potent Ca(2+)-dependent K+ channel blocker, inhibits the relaxation of guinea-pig tracheal smooth muscle induced by pituitary adenylate cyclase activating polypeptides with 27 residues (PACAP27) and with 38 residues (PACAP38). Two forms of PACAP were discovered in hypothalamic tissues, and are known to increase the tissues cyclic AMP levels and to be independent of beta-adrenoceptors. The relaxant effects of these polypeptides were evaluated by measuring the isometric tension of tracheal smooth muscle of guinea-pig in vitro. Both forms of PACAP showed dose-dependent relaxant effects. The pD2 of PACAP27 was 7.01 +/- 0.04 and that of PACAP38 was 6.43 +/- 0.05. ChTX (10(-12)-3 x 10(-9) mol/l) did not affect the resting tension of the guinea-pig tracheal smooth muscle. ChTX (10(-8) mol/l) slightly increased the tension, in some experiments being considered as a phasic tension change. ChTX (10(-8) mol/l) caused a small but significant rightward shift in the concentration-response curves of PACAP27 and PACAP38. ChTX decreased the pD2 of PACAP27 to 6.74 +/- 0.03 and that of PACAP38 to 6.25 +/- 0.04. These results suggest that cyclic AMP-mediated activation of Ca(2+)-dependent K+ channels may play an important role in the relaxation of the guinea-pig tracheal smooth muscle induced by both forms of PACAP as well as beta-agonist.