HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/G1170    most recent 00509.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Cao, W. Articles by Biancani, P. Search for Related Content PubMed PubMed Citation Articles by Cao, W. Articles by Biancani, P.

HORMONES AND SIGNALING

H₂O₂: a mediator of esophagitis-induced damage to calcium-release mechanisms in cat lower esophageal sphincter

¹Department of Medicine, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island; and ²Division of Biomolecular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts

Submitted 11 November 2004 ; accepted in final form 19 January 2005

We previously reported that induction of acute experimental esophagitis by repeated perfusion of HCl may affect release of intracellular Ca²⁺ stores. We therefore measured cytosolic Ca²⁺ in response to a maximally effective dose of ACh in fura 2-AM-loaded lower esophageal sphincter (LES) circular muscle cells and examined the contribution of H₂O₂ to the reduction in Ca²⁺ signal. In normal cells, the ACh-induced Ca²⁺ increase was the same in normal-Ca²⁺ and Ca²⁺-free medium and was abolished by the phosphatidylinositol 4,5-bisphosphate-specific phospholipase C inhibitor U-73122, confirming that the initial ACh-induced contraction depends on Ca²⁺ release from intracellular stores through production of inositol trisphosphate. In LES cells, the ACh-induced Ca²⁺ increase in normal-Ca²⁺ medium was significantly lower in esophagitis than in normal cells and was further reduced (70%) when the cells were incubated in Ca²⁺-free medium. This reduction was partially reversed by the H₂O₂ scavenger catalase. H₂O₂ measurements in LES circular muscle showed significantly higher levels in esophagitis than in normal cells. When normal LES cells were incubated with H₂O₂, the ACh-induced Ca²⁺ increase was significantly reduced in normal-Ca²⁺ and Ca²⁺-free medium and was similar to that observed in animals with esophagitis. The initial ACh-induced contraction was also reduced in normal cells incubated with H₂O₂. H₂O₂, when applied to cells at sufficiently high concentration, produced a visible and prolonged Ca²⁺ signal in normal cells. H₂O₂-induced cell contraction was also sensitive to depletion of stores by thapsigargin (TG); conversely, H₂O₂ reduced TG-induced contraction, suggesting that TG and H₂O₂ may operate through similar mechanisms. Ca²⁺-ATPase activity measurement indicates that H₂O₂ and TG reduced Ca²⁺-ATPase activity, confirming similarity of mechanism of action. We conclude that H₂O₂ may be at least partly responsible for impairment of Ca²⁺ release in acute experimental esophagitis by inhibiting Ca²⁺ uptake and refilling Ca²⁺ stores.

acetylcholine; smooth muscle

This article has been cited by other articles:

				P. Cong, Z.-L. Xiao, P. Biancani, and J. Behar Reactive oxygen species are messengers in maintenance of human and guinea pig gallbladder tonic contraction Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1244 - G1251. [Abstract] [Full Text] [PDF]

				W. Hu, S. Mahavadi, F. Li, and K. S. Murthy Upregulation of RGS4 and downregulation of CPI-17 mediate inhibition of colonic muscle contraction by interleukin-1 Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1991 - C2000. [Abstract] [Full Text] [PDF]

				W. Cao, L. Cheng, J. Behar, P. Biancani, and K. M. Harnett IL-1beta signaling in cat lower esophageal sphincter circular muscle Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G672 - G680. [Abstract] [Full Text] [PDF]

				Z.-L. Xiao, W. Cao, P. Biancani, and J. Behar Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): 1008 - 1015. [Abstract] [Full Text] [PDF]

				P. J. Gomez-Pinilla, S. Morales, C. Camello-Almaraz, R. Moreno, M. J. Pozo, and P. J. Camello Changes in guinea pig gallbladder smooth muscle Ca2+ homeostasis by acute acalculous cholecystitis Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G14 - G22. [Abstract] [Full Text] [PDF]

				L. Cheng, W. Cao, C. Fiocchi, J. Behar, P. Biancani, and K. M. Harnett In vitro model of acute esophagitis in the cat Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G860 - G869. [Abstract] [Full Text] [PDF]