Acute experimental esophagitis activates a second signal transduction pathway in cat smooth muscle from the lower esophageal sphincter.

  • Sohn U
  • Harnett K
  • Cao W
 et al. 
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Abstract

In single cells, isolated by enzymatic digestion from the circular muscle layer of the lower esophageal sphincter (LES), acute experimental esophagitis (AE) alters signal transduction in response to a maximally effective dose of acetylcholine. In normal LES contraction was inhibited by M3 > M1 or M2 antagonists. In AE inhibition by M2 antagonists increased significantly so that contraction was inhibited by M3 > M2 > M1 antagonists. In normal cells permeabilized by saponin, contraction was antagonized by antibodies against Gq/11, by the phosphatidylinositol-specific phospholipase C (PI-PLC) antagonist U 73122, but not by the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor D609, or by the phospholipase D pathway inhibitor propranolol. In AE contraction was reduced by Gq/11 and Gi3 antibodies and by U73122, propranolol and D609. After thapsigargin treatment of normal cells to reduce intracellular Ca++ stores, contraction was inhibited by M2 and M3 antagonists, by antibodies against Gq/11 and Gi3, by U73122, D609 and propranolol, suggesting that depletion of Ca++ stores reproduces the changes induced by AE. We conclude that in normal LES smooth muscle cells acetylcholine-induced contraction is mediated by M3 receptors linked to Gq/11 and PI-PLC, whereas in AE, contraction through this pathway is reduced, perhaps because of reduction in Ca++ stores, and a second pathway is activated by M2 receptors linked to Gi3, PC-PLC and phospholipase D.

Author-supplied keywords

  • Acetylcholine
  • Acetylcholine: pharmacology
  • Acute Disease
  • Animals
  • Calcium
  • Calcium: metabolism
  • Cats
  • Esophagitis
  • Esophagitis: physiopathology
  • Esophagogastric Junction
  • Esophagogastric Junction: physiopathology
  • Female
  • GTP-Binding Proteins
  • GTP-Binding Proteins: physiology
  • Male
  • Muscarinic
  • Muscarinic: physiology
  • Muscle
  • Muscle Contraction
  • Muscle Contraction: drug effects
  • Phospholipases
  • Phospholipases: physiology
  • Protein Kinase C
  • Protein Kinase C: physiology
  • Receptors
  • Signal Transduction
  • Smooth
  • Smooth: physiopathology

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  • ISSN: 0022-3565
  • PUI: 28016505
  • SGR: 0031471726
  • PMID: 9400005
  • SCOPUS: 2-s2.0-0031471726
  • ISBN: 9610704042

Authors

  • U D Sohn

  • K M Harnett

  • W Cao

  • H Rich

  • N Kim

  • J Behar

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