Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle

Nayoung Kim, W. Cao, Sung Song In Sung Song, Yong Kim Chung Yong Kim, Dong Sohn Uy Dong Sohn, K. M. Harnett, P. Biancani

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Abstract

Background and Aims: 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, G(i3) 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 G(q) 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 G(i3) proteins and phosphatidylcholine-specific phospholipase. In the LES, LTD4 activates a calmodulin-dependent pathway through pertussis toxin-insensitive G(q) 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.

Original languageEnglish
Pages (from-to)919-928
Number of pages10
JournalGastroenterology
Volume115
Issue number4
DOIs
StatePublished - 1 Jan 1998

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Leukotriene D4
Lower Esophageal Sphincter
Smooth Muscle
Cats
Pertussis Toxin
Protein Kinase C
Phosphoinositide Phospholipase C
Phospholipase D
Calmodulin
Esophagus
Acetylcholine
Heparin
Antibodies
Cholinergic Agonists
Inositol 1,4,5-Trisphosphate
Esophagitis
Phospholipases
Phospholipases A2
Diglycerides
Saponins

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Kim, N., Cao, W., In Sung Song, S. S., Chung Yong Kim, Y. K., Uy Dong Sohn, D. S., Harnett, K. M., & Biancani, P. (1998). Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Gastroenterology, 115(4), 919-928. https://doi.org/10.1016/S0016-5085(98)70264-1
Kim, Nayoung ; Cao, W. ; In Sung Song, Sung Song ; Chung Yong Kim, Yong Kim ; Uy Dong Sohn, Dong Sohn ; Harnett, K. M. ; Biancani, P. / Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. In: Gastroenterology. 1998 ; Vol. 115, No. 4. pp. 919-928.
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abstract = "Background and Aims: 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, G(i3) 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 G(q) 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 G(i3) proteins and phosphatidylcholine-specific phospholipase. In the LES, LTD4 activates a calmodulin-dependent pathway through pertussis toxin-insensitive G(q) 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.",
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Kim, N, Cao, W, In Sung Song, SS, Chung Yong Kim, YK, Uy Dong Sohn, DS, Harnett, KM & Biancani, P 1998, 'Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle', Gastroenterology, vol. 115, no. 4, pp. 919-928. https://doi.org/10.1016/S0016-5085(98)70264-1

Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. / Kim, Nayoung; Cao, W.; In Sung Song, Sung Song; Chung Yong Kim, Yong Kim; Uy Dong Sohn, Dong Sohn; Harnett, K. M.; Biancani, P.

In: Gastroenterology, Vol. 115, No. 4, 01.01.1998, p. 919-928.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle

AU - Kim, Nayoung

AU - Cao, W.

AU - In Sung Song, Sung Song

AU - Chung Yong Kim, Yong Kim

AU - Uy Dong Sohn, Dong Sohn

AU - Harnett, K. M.

AU - Biancani, P.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Background and Aims: 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, G(i3) 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 G(q) 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 G(i3) proteins and phosphatidylcholine-specific phospholipase. In the LES, LTD4 activates a calmodulin-dependent pathway through pertussis toxin-insensitive G(q) 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.

AB - Background and Aims: 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, G(i3) 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 G(q) 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 G(i3) proteins and phosphatidylcholine-specific phospholipase. In the LES, LTD4 activates a calmodulin-dependent pathway through pertussis toxin-insensitive G(q) 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.

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U2 - 10.1016/S0016-5085(98)70264-1

DO - 10.1016/S0016-5085(98)70264-1

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JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

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