title: Acute experimental esophagitis activates a second signal transduction pathway in cat smooth muscle from the lower esophageal sphincter.
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.
authors.affiliation: Department of Pharmacology, Chung Ang University Pharmacy College, Seoul 156-756, Korea.
authors.forename: U D
authors.initials: UD
authors.lastname: Sohn
authors.forename: K M
authors.initials: KM
authors.lastname: Harnett
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.forename: H
authors.initials: H
authors.lastname: Rich
authors.forename: N
authors.initials: N
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Behar
authors.forename: P
authors.initials: P
authors.lastname: Biancani
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D004941:Esophagitis / Q000503:physiopathology*; D004943:Esophagogastric Junction / Q000503:physiopathology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000503:physiopathology*; D010740:Phospholipases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction
chemical_list: D011976:Receptors, Muscarinic; D011493:Protein Kinase C; D010740:Phospholipases; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium