title: Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle.
abstract: OBJECTIVE
  In esophageal circular muscle, acetylcholine activates phosphatidylcholine-specific phospholipases C and D and phospholipase A2, producing diacylglycerol and arachidonic acid, which cause contraction by interacting synergistically to activate protein kinase C. In a model of acute esophagitis, leukotriene D4 (LTD4) contributes to acetylcholine-induced contraction. We examined intracellular signaling in LTD4-induced contraction.
  
  
  METHODS
  Esophageal and lower esophageal sphincter (LES) cells, isolated by enzymatic digestion, were contracted by LTD4 in the absence or presence of inhibitors. Permeabilization by saponin allowed use of G-protein antibodies and heparin.
  
  
  RESULTS
  Esophageal contraction was inhibited by pertussis toxin, Gi3 antibodies, D609 (phosphatidylcholine-specific phospholipase C inhibitor), propranolol (phospholipase D pathway inhibitor), and chelerythrine (protein kinase C antagonist) but not W7 (calmodulin antagonist). LES contraction was unaffected by pertussis toxin. It was inhibited by Gq antibodies, U-73122 (phosphatidylinositol-specific phospholipase C inhibitor), heparin (inositol 1,4,5-trisphosphate inhibitor), and W7 and reduced by D609.
  
  
  CONCLUSIONS
  In the esophagus, LTD4 activates a protein kinase C-dependent pathway through pertussis toxin-sensitive Gi3 proteins and phosphatidylcholine-specific phospholipase. In the LES, LTD4 activates a calmodulin-dependent pathway through pertussis toxin-insensitive Gq proteins and phosphatidylinositol-specific phospholipase C. The intracellular pathways activated by LTD4 in the esophagus and the LES are similar to those activated by acetylcholine and other agonists.
authors.affiliation: Department of Internal Medicine, Kangnam General Hospital, Public Corporation, Seoul, Korea.
authors.forename: N
authors.initials: N
authors.lastname: Kim
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.forename: I S
authors.initials: IS
authors.lastname: Song
authors.forename: C Y
authors.initials: CY
authors.lastname: Kim
authors.forename: U D
authors.initials: UD
authors.lastname: Sohn
authors.forename: K M
authors.initials: KM
authors.lastname: Harnett
authors.forename: P
authors.initials: P
authors.lastname: Biancani
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000502:physiology; D002415:Cats; D004943:Esophagogastric Junction / Q000187:drug effects*; D004947:Esophagus / Q000187:drug effects*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D017998:Leukotriene D4 / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology; D010740:Phospholipases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology
chemical_list: D002147:Calmodulin; D010716:Phosphatidylinositols; D017998:Leukotriene D4; D011493:Protein Kinase C; D010740:Phospholipases; D019204:GTP-Binding Proteins