ryanodine and tyrphostin-25

The aim of this study was to investigate the signal transduction mechanisms underlying the inhibitory effect induced by pituitary adenylate cyclase activating peptide (PACAP-27) on the spontaneous contractile activity of longitudinal muscle of mouse ileum. Mechanical activity of ileal segments 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 localised Ca2+ release from intracellular stores, which could provide the opening of apamin-sensitive Ca2+-dependent K+ channels.

Topics: Adenine; Adenylyl Cyclase Inhibitors; Animals; Apamin; Boron Compounds; Calcium; Calcium-Transporting ATPases; Dose-Response Relationship, Drug; Enzyme Inhibitors; Estrenes; Genistein; Ileum; In Vitro Techniques; Indoles; Male; Mice; Mice, Inbred C57BL; Muscle Contraction; Muscle, Smooth; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Phosphodiesterase Inhibitors; Pituitary Adenylate Cyclase-Activating Polypeptide; Protein-Tyrosine Kinases; Pyrrolidinones; Ryanodine; Thapsigargin; Tyrphostins; Vasodilator Agents