Store-operated calcium influx in human gastric cells: Role of endogenous prostaglandins

E. R. Kokoska, G. S. Smith, T. A. Miller, D. W. Mercer, D. I. Soybel, J. B. Matthews

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background. Store-operated calcium influx (SOCI) appears to be a key component in regulating processes such as gene expression and cellular metabolism in nonexcitable cells. Our objective was to determine what effect, if any, prostaglandin inhibition had on SOCI in human gastric cells. Methods. SOCI was induced in human gastric cells (AGS) with thapsigargin, a microsomal Ca++ adenosine triphosphatase inhibitor. Quantitation of SOCI was achieved by two different methods: sustained intracellular calcium elevation and manganese (Mn++) uptake. Endogenous prostaglandin E2 (PGE2) synthesis was measured by enzyme immunoassay. Three different nonsteroidal anti- inflammatory drugs (NSAIDs; indomethacin, ibuprofen, and aspirin) were used to minimize the nonspecific actions of any individual agent. Results. SOCI in AGS cells was inhibited by the store-operated Ca++ Channel blocker lanthanum (La+++) but not the voltage-operated Ca++ channel antagonists verapamil or nifedipine. Each of the three NSAIDs equally inhibited SOCI. The inhibition of SOCI induced by indomethacin was partially reversed by the addition of exogenous PGE2. Finally, AGS cells exposed to thapsigargin demonstrated significantly increased endogenous PGE2 release. Conclusions. These data suggest that NSAIDs inhibit (or endogenous prostaglandins modulate) SOCI in human gastric cells, at least in part. Because SOCI appears to be a critical mechanism involved in cell proliferation, this may provide one explanation of how NSAIDs inhibit (and endogenous prostaglandins enhance) gastric epithelial renewal and repair.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalSurgery
Volume124
Issue number2
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Surgery

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    Kokoska, E. R., Smith, G. S., Miller, T. A., Mercer, D. W., Soybel, D. I., & Matthews, J. B. (1998). Store-operated calcium influx in human gastric cells: Role of endogenous prostaglandins. Surgery, 124(2), 429-437. https://doi.org/10.1016/S0039-6060(98)70150-3