Experimental esophagitis affects intracellular calcium stores in the cat lower esophageal sphincter

Harlan Rich, Uy Dong Sohn, Jose Behar, Nayoung Kim, Piero Biancani

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

Abstract

We previously showed that lower esophageal spincter (LES) tone depends on spontaneous production of inositol 1,4,5-trisphosphate (IP3) and release of intracellular Ca2+ and that acute experimental esophagitis reduces LES tone and IP3 production, suggesting damage to mechanisms responsible for release of Ca2+ from intracellular stores. In the present investigation, we examined the possibility that mechanisms responsible for Ca2+ storage or uptake may also be damaged. LES circular muscle cells were isolated by enzymatic digestion. Contraction was measured in response to IP3 and thapsigargin, which enhances release of Ca2+ from intracellular stores, and in response to calmodulin and to diacylglycerol. In addition, normal cells were incubated in thapsigargin to assess the effect of depletion of intracellular Ca2+ stores on contractile response. Contraction in response to IP3 and thapsigargin was reduced in experimental esophagitis, but contraction in response to calmodulin or diacylglycerol was not. Acetylcholine (ACh)-induced contraction of normal cells was inhibited by the calmodulin antagonist CGS-9343B but not by 1-(5-isoquinolinesulfonyl)-2- methyl-piperazine dihydrochloride (H-7). In contrast, in cells from animals with esophagitis or in thapsigargin-treated cells from normal animals, ACh- induced contraction was inhibited by H-7 and not by CGS-9343B. We conclude that experimental esophagitis may damage intracellular Ca2+ stores in the LES and change the intracellular contractile pathways activated by ACh from calmodulin dependent in normal cells to protein kinase C dependent in esophagitis.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume272
Issue number6 35-6
StatePublished - 1 Jun 1997

Fingerprint

Lower Esophageal Sphincter
Esophagitis
Thapsigargin
Calmodulin
Cats
Calcium
Acetylcholine
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Diglycerides
Inositol 1,4,5-Trisphosphate
Muscle Cells
Protein Kinase C
Digestion

Keywords

  • Calmodulin
  • Diacylglycerol
  • Esophagitis peptic
  • Esophagogastric junction
  • Esophagus
  • Inositol phosphates
  • Muscle smooth
  • Phosphatidylinositol
  • Phosphoinositides
  • Protein kinase C
  • Second messenger systems
  • Terpenes

Cite this

@article{a6002885c3374c61b62ae5f8f5aacfbb,
title = "Experimental esophagitis affects intracellular calcium stores in the cat lower esophageal sphincter",
abstract = "We previously showed that lower esophageal spincter (LES) tone depends on spontaneous production of inositol 1,4,5-trisphosphate (IP3) and release of intracellular Ca2+ and that acute experimental esophagitis reduces LES tone and IP3 production, suggesting damage to mechanisms responsible for release of Ca2+ from intracellular stores. In the present investigation, we examined the possibility that mechanisms responsible for Ca2+ storage or uptake may also be damaged. LES circular muscle cells were isolated by enzymatic digestion. Contraction was measured in response to IP3 and thapsigargin, which enhances release of Ca2+ from intracellular stores, and in response to calmodulin and to diacylglycerol. In addition, normal cells were incubated in thapsigargin to assess the effect of depletion of intracellular Ca2+ stores on contractile response. Contraction in response to IP3 and thapsigargin was reduced in experimental esophagitis, but contraction in response to calmodulin or diacylglycerol was not. Acetylcholine (ACh)-induced contraction of normal cells was inhibited by the calmodulin antagonist CGS-9343B but not by 1-(5-isoquinolinesulfonyl)-2- methyl-piperazine dihydrochloride (H-7). In contrast, in cells from animals with esophagitis or in thapsigargin-treated cells from normal animals, ACh- induced contraction was inhibited by H-7 and not by CGS-9343B. We conclude that experimental esophagitis may damage intracellular Ca2+ stores in the LES and change the intracellular contractile pathways activated by ACh from calmodulin dependent in normal cells to protein kinase C dependent in esophagitis.",
keywords = "Calmodulin, Diacylglycerol, Esophagitis peptic, Esophagogastric junction, Esophagus, Inositol phosphates, Muscle smooth, Phosphatidylinositol, Phosphoinositides, Protein kinase C, Second messenger systems, Terpenes",
author = "Harlan Rich and Sohn, {Uy Dong} and Jose Behar and Nayoung Kim and Piero Biancani",
year = "1997",
month = "6",
day = "1",
language = "English",
volume = "272",
journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "6 35-6",

}

Experimental esophagitis affects intracellular calcium stores in the cat lower esophageal sphincter. / Rich, Harlan; Sohn, Uy Dong; Behar, Jose; Kim, Nayoung; Biancani, Piero.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 272, No. 6 35-6, 01.06.1997.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Experimental esophagitis affects intracellular calcium stores in the cat lower esophageal sphincter

AU - Rich, Harlan

AU - Sohn, Uy Dong

AU - Behar, Jose

AU - Kim, Nayoung

AU - Biancani, Piero

PY - 1997/6/1

Y1 - 1997/6/1

N2 - We previously showed that lower esophageal spincter (LES) tone depends on spontaneous production of inositol 1,4,5-trisphosphate (IP3) and release of intracellular Ca2+ and that acute experimental esophagitis reduces LES tone and IP3 production, suggesting damage to mechanisms responsible for release of Ca2+ from intracellular stores. In the present investigation, we examined the possibility that mechanisms responsible for Ca2+ storage or uptake may also be damaged. LES circular muscle cells were isolated by enzymatic digestion. Contraction was measured in response to IP3 and thapsigargin, which enhances release of Ca2+ from intracellular stores, and in response to calmodulin and to diacylglycerol. In addition, normal cells were incubated in thapsigargin to assess the effect of depletion of intracellular Ca2+ stores on contractile response. Contraction in response to IP3 and thapsigargin was reduced in experimental esophagitis, but contraction in response to calmodulin or diacylglycerol was not. Acetylcholine (ACh)-induced contraction of normal cells was inhibited by the calmodulin antagonist CGS-9343B but not by 1-(5-isoquinolinesulfonyl)-2- methyl-piperazine dihydrochloride (H-7). In contrast, in cells from animals with esophagitis or in thapsigargin-treated cells from normal animals, ACh- induced contraction was inhibited by H-7 and not by CGS-9343B. We conclude that experimental esophagitis may damage intracellular Ca2+ stores in the LES and change the intracellular contractile pathways activated by ACh from calmodulin dependent in normal cells to protein kinase C dependent in esophagitis.

AB - We previously showed that lower esophageal spincter (LES) tone depends on spontaneous production of inositol 1,4,5-trisphosphate (IP3) and release of intracellular Ca2+ and that acute experimental esophagitis reduces LES tone and IP3 production, suggesting damage to mechanisms responsible for release of Ca2+ from intracellular stores. In the present investigation, we examined the possibility that mechanisms responsible for Ca2+ storage or uptake may also be damaged. LES circular muscle cells were isolated by enzymatic digestion. Contraction was measured in response to IP3 and thapsigargin, which enhances release of Ca2+ from intracellular stores, and in response to calmodulin and to diacylglycerol. In addition, normal cells were incubated in thapsigargin to assess the effect of depletion of intracellular Ca2+ stores on contractile response. Contraction in response to IP3 and thapsigargin was reduced in experimental esophagitis, but contraction in response to calmodulin or diacylglycerol was not. Acetylcholine (ACh)-induced contraction of normal cells was inhibited by the calmodulin antagonist CGS-9343B but not by 1-(5-isoquinolinesulfonyl)-2- methyl-piperazine dihydrochloride (H-7). In contrast, in cells from animals with esophagitis or in thapsigargin-treated cells from normal animals, ACh- induced contraction was inhibited by H-7 and not by CGS-9343B. We conclude that experimental esophagitis may damage intracellular Ca2+ stores in the LES and change the intracellular contractile pathways activated by ACh from calmodulin dependent in normal cells to protein kinase C dependent in esophagitis.

KW - Calmodulin

KW - Diacylglycerol

KW - Esophagitis peptic

KW - Esophagogastric junction

KW - Esophagus

KW - Inositol phosphates

KW - Muscle smooth

KW - Phosphatidylinositol

KW - Phosphoinositides

KW - Protein kinase C

KW - Second messenger systems

KW - Terpenes

UR - http://www.scopus.com/inward/record.url?scp=0030753129&partnerID=8YFLogxK

M3 - Article

VL - 272

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 6 35-6

ER -