Reversibility of deoxycholate-induced cellular hypercalcemia in rabbit gastric mucosal cells

M. Molloy, S. Batzri, A. J. Dziki, W. J. Goldberg, D. A. Hale, J. W. Harmon

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Bile acid exposure produces cellular hypercalcemia in gastric and hepatic cells. It is not known, however, whether this event contributes to cell injury or if it results from passive equilibration of calcium ion concentrations across the membranes of irreversibly damaged cells. This study was performed to determine whether the cellular hypercalcemia produced by bile acid exposure in gastric cells is reversible and to determine whether the source of this hypercalcemia is from intracellular stores of calcium, extracellular sources, or both. Methods. Cytosolic free calcium concentrations ([Ca](i)) were measured in rabbit gastric mucosal cells that had been loaded with the intracellular probe FURA-2. Measurements were performed in suspensions of dispersed cells by using standard spectrofluorometry and in primarily cultured cells by using fluorescence videomicroscopy. Measurements were made before and after exposure to 0.2, 0.5, and 1.0 mmol/L deoxycholic acid (DC). These measurements were made in the presence of 1 mmol/L extracellular calcium and in the absence of any extracellular calcium (0.5 mmol/L EGTA). Results. In experiments with dispersed cells and spectrofluorometry, [Ca](i) increased from a pretreatment level of 194 ± 8 nmol/L to 396 ± 21 nmol/L within 3 minutes of exposure to 0.2 mmol/L DC. When these cells were washed and resuspended in DC-free medium, [Ca](i)] decreased to 180 ± 5 nmol/L. In experiments with cultured cells and fluorescence videomicroscopy, rapid, reversible hypercalcemia was observed after exposure to 0.5 and 1.0 mmol/L DC. Removal of extracellular calcium from the incubating medium reduced both the magnitude and duration of the observed hypercalcemia. Conclusions. These data show that the cellular hypercalcemia that accompanies DC-induced injury in gastric cells is a reversible event. The initial increase in [Ca](i) appears to come from both intracellular and extracellular sources, although sustained hypercalcemia requires a source of extracellular calcium. As a reversible event, cellular hypercalcemia may be an important pathophysiologic feature of bile acid induced injury of the upper gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)89-97
Number of pages9
JournalSurgery
Volume119
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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