Mechanisms underlying the inhibitory effects induced by pituitary adenylate cyclase-activating peptide in mouse ileum

The aim of this study was to investigate the signal transduction mechanisms underlying the inhibitory effect induced by pituitary adenylatecyclase activating peptide (PACAP-27) on the spontaneous contractile activity of longitudinal muscle of mouse ileum. Mechanical activity of ilealsegments was recorded isometrically in vitro. PACAP-27 produced apamin-sensitive reduction of the amplitude of the spontaneous contractions.9-(Tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), adenylate cyclase inhibitor, or genistein and tyrphostin 25, tyrosine kinase inhibitors,had negligible effects on PACAP-27-induced inhibition. PACAP-27 effects were significantly inhibited by U-73122, phopholipase C (PLC)inhibitor, by 2-aminoethoxy-diphenylborate (2-APB), permeable blocker of inositol 1,4,5-triphosphate (IP3) receptors and by depletion of Ca2+stores with cyclopiazonic acid or thapsigargin. Ryanodine did not reduce PACAP-27-inhibitory responses.We suggest that, in mouse ileum, the inhibitory responses to PACAP-27 involve stimulation of PLC, increased production of IP3 and localisedCa2+ release from intracellular stores, which could provide the opening of apamin-sensitive Ca2+-dependent K+ channels.