The effects of PACAP and VIP on guinea pig tracheal smooth muscle in vitro

Neither pituitary adenylate cyclase activating polypeptide-38 (PACAP) nor its homologue, vasoactive intestinal polypeptide (VIP), contracted guinea pig isolated trachea (GPT), but on preparations contracted with KCl (40 mM), both caused concentration-related relaxation (3 nM-3 microM, VIP IC50 = 72 nM, PACAP IC50 = 224 nM). Relaxant curves to PACAP were slower in reaching a maximum than those to VIP (approximately 150 and 50 min, respectively). The protease inhibitors, phosphoramidon (1 microM), leupeptin (50 microM), bestatin (100 microM), soya bean trypsin inhibitor (1 microM), and aprotinin (5 microM), together caused a small enhancement of relaxations to VIP, but not to PACAP. The VIP antagonist, [4-Cl-D-Phe6, Leu17]VIP (1-10 microM), did not inhibit the relaxation to either peptide, but did cause large contractions, which were enhanced by protease inhibition. These findings demonstrate that PACAP relaxes GPT in a similar manner to VIP.