Inhibition of Na+-coupled solute transport by calcium in brush border membrane vesicles.

Intracellular Ca++ is known to influence Na+ flux in luminal membranes. Abnormally elevated Ca++ levels in some cells is believed to be the primary pathophysiologic defect in cystic fibrosis (CF). This in turn is thought to alter Na+ transport which accounts for certain clinical manifestations of this disease. Two Na+-dependent intestinal transport mechanisms have been reported to be suppressed or missing in CF. To examine whether alterations in cell Ca++ may account for these findings, studies were performed to examine the influence of Ca++ on Na+-solute co-transport across intestinal luminal membranes. Purified brush border membrane vesicles prepared from rat small bowel were preincubated in either Ca++-free buffer or buffer containing 2.5 mM CaCl2. Ca++ loaded vesicles showed marked inhibition of Na+ co-transport of taurocholic acid, taurochenodeoxycholic acid, glucose and valine when compared to controls. The uptake of Na+ was also significantly reduced by intravesicular Ca++. These data demonstrate that intravesicular Ca++ inhibits Na+-coupled solute transport as well as Na+ influx across intestinal brush border membranes. These data suggest that intracellular Ca++ may suppress Na+-dependent solute absorption in the intestine. Results presented here further support the theory that elevated intracellular Ca++ may account for intestinal malabsorption and other altered transport phenomena reported in CF.