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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine / analogs & derivatives
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Adenine / pharmacology
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Adenylyl Cyclase Inhibitors
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Animals
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Apamin / pharmacology
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Boron Compounds / pharmacology
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Calcium / metabolism
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Calcium-Transporting ATPases / antagonists & inhibitors
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Genistein / pharmacology
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Ileum / drug effects*
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Ileum / physiology
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In Vitro Techniques
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Indoles / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Muscle Contraction / drug effects*
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Muscle, Smooth / drug effects
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Muscle, Smooth / metabolism
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Muscle, Smooth / physiology
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Phosphodiesterase Inhibitors / pharmacology
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Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Pyrrolidinones / pharmacology
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Ryanodine / pharmacology
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Thapsigargin / pharmacology
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Tyrphostins / pharmacology
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Vasodilator Agents / pharmacology
Substances
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Adenylyl Cyclase Inhibitors
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Boron Compounds
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Enzyme Inhibitors
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Estrenes
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Indoles
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Phosphodiesterase Inhibitors
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Pyrrolidinones
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Tyrphostins
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Vasodilator Agents
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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tyrphostin 25
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Ryanodine
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9-(tetrahydro-2-furyl)-adenine
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Apamin
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Thapsigargin
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Genistein
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2-aminoethoxydiphenyl borate
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Nitric Oxide Synthase
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Protein-Tyrosine Kinases
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Calcium-Transporting ATPases
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Adenine
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Calcium
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NG-Nitroarginine Methyl Ester
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cyclopiazonic acid