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

6533b856fe1ef96bd12b27c7

RESEARCH PRODUCT

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

Rosa Serio Flavia Mulè Maria-grazia Zizzo

subject

Male Indoles Phosphodiesterase Inhibitors Vasodilator Agents Mouse ileum Stimulation Settore BIO/09 - Fisiologia Mice chemistry.chemical_compound Inositol Enzyme Inhibitors Estrenes Ryanodine Ryanodine receptor Protein-Tyrosine Kinases Tyrphostins Genistein Pyrrolidinones Cell biology Pituitary adenylate cyclase-activating peptide NG-Nitroarginine Methyl Ester Pituitary Adenylate Cyclase-Activating Polypeptide Thapsigargin Signal transduction Cyclopiazonic acid hormones hormone substitutes and hormone antagonists Muscle Contraction Boron Compounds endocrine system medicine.medical_specialty Thapsigargin Muscular inhibition Calcium-Transporting ATPases In Vitro Techniques Inositol 1 4 5-triphosphate Biology PACAP-27 (pituitary adenylate cyclase activating peptide)Ileum Phospholipase C Internal medicine medicine Animals Pharmacology Dose-Response Relationship Drug Phospholipase C Adenine Muscle Smooth Mice Inbred C57BL Endocrinology Apamin chemistry Adenylyl Cyclase Inhibitors Calcium Nitric Oxide Synthase

description

Abstract 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.

year	journal	country	edition	language
2005-08-02	European Journal of Pharmacology

https://doi.org/10.1016/j.ejphar.2005.08.027