Ricinoleate and deoxycholate are calcium ionophores in jejunal brush border vesicles

Abstract

The intestinal secretagogues ricinoleate and deoxycholate have been tested for a capacity to form complexes with Ca2+ ions and to affect the passive equilibration of Ca2+ ions across the jejunal brush border membrane. Both of these agents formed butanol-soluble Ca2+ complexes in a model phase distribution system. They also promote the passive uptake and efflux of Ca2+ across brush border vesicles in a concentration-dependent manner. The levels of ricinoleate and deoxycholate that increase the rate of transvesicular Ca2+ movement are in the 100 to 300 microM range. Concentrations as high as 1.0 mM had no significant detergent effects in vesicles as measured by release of entrapped sorbitol. The kinetics of Ca2+ uptake and efflux are similar in brush border vesicles treated with A23187, ricinoleate, or deoxycholate. The influx rates observed in this study were high enough to cause the collapse of a Ca2+ gradient, which had been generated by Ca--Mg ATPase enzyme activity in the brush border membrane. Ricinoleate did not affect Ca--Mg ATPase activity at concentrations used in this study, but deoxycholate was inhibitory, indicating two potential modes for elevation of intracellular Ca2+ content by deoxycholate. When compared with the effects of the Ca2+ ionophore, A23187, it appears that both ricinoleate and deoxycholate could have significant intestinal secretory activity due to this Ca2+ ionophore property. It is also noteworthy that, at least in this model system, potential secretory effects are expressed at concentrations significantly below levels that have been associated with detergent effects or altered epithelial morphology.