REVERSIBILITY OF DEOXYCHOLATE-INDUCED CELLULAR HYPERCALCEMIA IN RABBIT GASTRIC-MUCOSAL CELLS

Background. Bile acid exposure produces cellular hypercalcemia in gast ric and hepatic cells. It is not Known, however, whether this event co ntributes to cell injury or if it results from passive equilibration o f calcium ion concentrations across the membranes of irreversibly dama ged cells. This study was performed to determine whether the cellular hypercalcemia produced by bile acid exposure in gastric cells is rever sible and to determine whether the source of this hypercalcemia is fro m intracellular stores of calcium extracellular sources, or both. Meth ods. Cytosolic free calcium concentrations ([Ca](i)) were measured in rabbit gastric mucosal cells that had been loaded with the intracellul ar probe FURA-2. Measurements were performed in suspensions of dispers ed cells by using standard spectrofluorometry and in primarily culture d 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 extrac ellular calcium and in the absence of any extracellular calcium (0.5 m mol/L EGTA). Results. In experiments with dispersed cells and spectrof luorometry, [Ca](i) increased from a pretreatment level of 194 +/- 8 n mol/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, [C a](i)] decreased to 180 +/- 5 nmol/L. In experiments with cultured cel ls and florescence videomicroscopy, rapid, reversible hypercalcemia wa s observed after exposure to 0.5 and 1.0 mmol/L DC. Removal of extrace llular calcium from the incubating medium reduced both the magnitude a nd duration of the observed hypercalcemia. Conclusions. These data sho w that the cellular hypercalcemia that accompanies DC-induced injury i n gastric cells is a reversible event. The initial increase in [Ca](i) appears to come from both intracellular and extracellular sources, al though sustained hypercalcemia requires a source of extracellular calc ium. As a reversible event, cellular hypercalcemia may be an important pathophysiologic feature of bile and induced injury of the upper gast rointestinal tract.