PMID- 15662047
OWN - NLM
STAT- MEDLINE
DCOM- 20050621
LR  - 20131121
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 288
IP  - 6
DP  - 2005 Jun
TI  - H(2)O(2): a mediator of esophagitis-induced damage to calcium-release mechanisms 
      in cat lower esophageal sphincter.
PG  - G1170-8
AB  - We previously reported that induction of acute experimental esophagitis by 
      repeated perfusion of HCl may affect release of intracellular Ca(2+) stores. We 
      therefore measured cytosolic Ca(2+) 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 H(2)O(2) to the reduction in Ca(2+) signal. In 
      normal cells, the ACh-induced Ca(2+) increase was the same in normal-Ca(2+) and 
      Ca(2+)-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 Ca(2+) release from intracellular 
      stores through production of inositol trisphosphate. In LES cells, the 
      ACh-induced Ca(2+) increase in normal-Ca(2+) medium was significantly lower in 
      esophagitis than in normal cells and was further reduced ( approximately 70%) 
      when the cells were incubated in Ca(2+)-free medium. This reduction was partially 
      reversed by the H(2)O(2) scavenger catalase. H(2)O(2) measurements in LES 
      circular muscle showed significantly higher levels in esophagitis than in normal 
      cells. When normal LES cells were incubated with H(2)O(2), the ACh-induced Ca(2+) 
      increase was significantly reduced in normal-Ca(2+) and Ca(2+)-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 H(2)O(2). H(2)O(2), 
      when applied to cells at sufficiently high concentration, produced a visible and 
      prolonged Ca(2+) signal in normal cells. H(2)O(2)-induced cell contraction was 
      also sensitive to depletion of stores by thapsigargin (TG); conversely, H(2)O(2) 
      reduced TG-induced contraction, suggesting that TG and H(2)O(2) may operate 
      through similar mechanisms. Ca(2+)-ATPase activity measurement indicates that 
      H(2)O(2) and TG reduced Ca(2+)-ATPase activity, confirming similarity of 
      mechanism of action. We conclude that H(2)O(2) may be at least partly responsible 
      for impairment of Ca(2+) release in acute experimental esophagitis by inhibiting 
      Ca(2+) uptake and refilling Ca(2+) stores.
FAU - Cao, Weibiao
AU  - Cao W
AD  - Dept. of Medicine, Brown Medical School and Rhode Island Hospital, 
      Gastrointestinal Motor Function Research Laboratory, 55 Claverick St., Rm. 333, 
      Providence, RI 02903, USA.
FAU - Harnett, Karen M
AU  - Harnett KM
FAU - Cheng, Ling
AU  - Cheng L
FAU - Kirber, Michael T
AU  - Kirber MT
FAU - Behar, Jose
AU  - Behar J
FAU - Biancani, Piero
AU  - Biancani P
LA  - eng
GR  - R01-DK-57030/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050120
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Oxidants)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - N9YNS0M02X (Acetylcholine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Acetylcholine/*pharmacology
MH  - Animals
MH  - Calcium/*pharmacokinetics
MH  - Cats
MH  - Cell Culture Techniques
MH  - Cytosol/chemistry
MH  - Disease Models, Animal
MH  - Esophagitis/*physiopathology/veterinary
MH  - Esophagus/*pathology/*physiology
MH  - Female
MH  - Hydrogen Peroxide/*pharmacology
MH  - Male
MH  - Muscle Contraction
MH  - Muscle, Smooth/physiology
MH  - Oxidants/*pharmacology
MH  - Signal Transduction
EDAT- 2005/01/22 09:00
MHDA- 2005/06/23 09:00
CRDT- 2005/01/22 09:00
PHST- 2005/01/22 09:00 [pubmed]
PHST- 2005/06/23 09:00 [medline]
PHST- 2005/01/22 09:00 [entrez]
AID - 00509.2004 [pii]
AID - 10.1152/ajpgi.00509.2004 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2005 Jun;288(6):G1170-8. doi: 
      10.1152/ajpgi.00509.2004. Epub 2005 Jan 20.