Summary
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 concentrationdependent manner. The levels of ricinoleate and deoxycholate that increase the rate of transvesicular Ca2+ movement are in the 100 to 300 μm range. Concentrations as high as 1.0mm 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.
Similar content being viewed by others
References
Abramson, J.J., Shamoo, A.E. 1979. Anionic detergents as divalent cation ionophores across black lipid membranes.J. Membrane Biol. 50:241–255
Adams, H. 1963. Adenosine 5′-triphosphate, determination with phosphoglycerate kinase.In: Methods of Enzymatic Analysis. H.U. Bergmeyer, editor. pp. 539–543. Verlag Chemie Academic Press, New York
Ammon, H.V., Phillips, S.F. 1973. Inhibition of colonic water and electrolyte absorption by fatty acids in manGastroenterology 65:774–749
Beubler, E., Juan, H. 1977. The function of prostaglandins in transmucosal water movement and blood flow in the rat jejunum.Naunyn-Schmiedeberg's Arch. Pharmacol. 299:89–94
Beubler, E., Juan, H. 1979. Effect of ricinoleic acid and other laxatives on net water flux and prostaglandin E release by the rat colon.J. Pharm. Pharmacol. 31:681–685
Binder, J.H. 1980. Pathophysiology of bile acid- and fatty acid-induced diarrhea.In: Secretory Diarrhea. M. Field, J.S. Fordtran, and G.G. Schultz, editors. pp. 154–178. American Physiological Society, Bethesda
Binder, J.H., Filburn, J.C., Volpe, B.T. 1972. Bile salt alteration of colonic electrolyte transport: Role of cyclic adenosine monophosphate.Gastroenterology 68:503–508
Bolton, J.E., Field, M. 1977. Ca ionophore-stimulated ion secretion in rabbit ileal mucosa: Relation to actions of cyclic 3′,5′-AMP and carbamylcholine.J. Membrane Biol. 35:159–174
Bradford, M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding.Anal. Biochem. 72:248–251
Bright-Asare, P., Binder, H.J. 1973. Stimulation of colonic secretion of water and electrolytes by hydroxy fatty acids.Gastroenterology 64:81–88
Cline, W.S., Lorenzsonn, V., Benz, L., Bass, P., Olsen, W.A. 1976. The effects of sodium ricinoleate on small intestinal function and structure.J. Clin. Invest 58:380–390
Cooperstein, S.J., Lazarow, A. 1951. A microspectrophotometric method for the determination of cytochrome oxidase.J. Biol. Chem. 189:665–670
Field, M. 1979. Intracellular mediators of secretion in the small intestine.In: Mechanisms of Intestinal Secretion. J.H. Binder, editor. pp. 83–91. Alan R. Loss, New York
Frizzell, R.A. 1977. Active chloride secretion by rabbit colon: Calcium-dependent stimulation by ionophore A23187.J. Membrane Biol. 35:175–187
Gaginella, T.S., Chadwick, V.S., Debongnie, J.C., Lewis, J.C., Phillips, S.F. 1977. Perfusion of rabbit colon with ricinoleic acid: Dose-related mucosal injury, fluid secretion, and increased permeability.Gastroenterology 73:45–101
Gaginella, T.S., Phillips, S.F., Dozois, R.R., Go, V.L.W. 1978. Stimulation of adenylate cyclase in homogenates of isolated intestinal epithelial cells from hamsters.Gastroenterology 74:11–15
Ghijsen, W.E.J.M., Van Os, C.H. 1979. Ca-stimulation ATPase in brush border and basolateral membranes of rat duodenum with high affinity sites for Ca ions.Nature (London) 274:802–803
Goerg, K.J., Gross, M., Nell, G., Rummel, W., Schultz, L. 1980. Comparative study of the effects of cholera toxin and sodium deoxycholate on the paracellular permeability and on net fluid and electrolyte transfer in the rat colon.Naunyn-Schmiedeberg's Arch. Pharmacol. 312:91–97
Hearn, P.R., Russell, R.G.G. 1977. Uptake of calcium by membrane vesicles isolated from pig duodenal brush borders and its release by ATP.In: Calcium Binding Proteins and Calcium Function. R.J. Wasserman, R.A. Corradino, E. Carafoli, R.H. Kretsinger, D.H. MacLenna, and F.L. Giegel, editors. pp. 370–372. North-Holland, New York
Helenius, A., Fries, E., Garoff, H., Simons, K. 1976. Solubilization of the semiliki forest virus membrane with sodium deoxycholate.Biochim. Biophys. Acta 436:319–322
Hopfer, V., Nelson, K., Penotto, J., Isselbacher, K.J. 1973. Glucose transport in isolated brush border membrane from rat small intestine.J. Biol. Chem. 248:25–32
Juan, H. 1981. Release of prostaglandins E2, I2, and D2 from perfused rabbit vascular tissue stimulated by ricinoleic acid.Prostaglandins Med. 7:209–215
Kelly, D.G., Kerlin, P., Sarr, M.G., Phillips, S.J. 1981. Ricinoleic acid causes secretion in autotransplanted (extrinsically denervated) canine jejunum.Dig. Dis. Sci. 26:966–970
Kessler, M., Acuto, O., Storelli, C., Murer, H., Muller, M., Semenza, G. 1978. A modified procedure for the rapid preparation of efficiently transporting vesicles from small intestinal brush border membranes.Biochim. Biophys. Acta 506:136–154
Kurebe, M. 1978. Effect of deoxycholate on Ca2+-ATPase of intestinal brush border membrane.Biochem. Pharmacol. 27:1961–1965
Parkinson, D.K., Ebel, H., Dibona, D.R., Sharp, G.W. 1972. Localization of action of cholera toxin on adenylcyclase in epithelial cells of rabbit intestine.J. Clin. Invest. 51:2292–2298
Pressman, B.C. 1968. Ionophore antibiotics as models for biological transport.Fed. Proc. 27:1283–1288
Racusen, L.C., Binder, H.J. 1979. Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat.J. Clin. Invest. 63:743–749
Rubin, R.P. 1978. Prostaglandins and calcium-membrane interactions in secretory glands.Ann. N.Y. Acad. Sci. 307:377–390
Schwartz, S.E., Stauffer, J.Q., Burgess, L.W., Chaney, M. 1980. Oxalate uptake by everted sacs of rat colon: Regional differences and the effects of pH and ricinoleic acid.Biochim. Biophys. Acta 595:404–413
Sottocasa, G.L., Kuylenstuerna, B., Ernster, L., Bergstrand, A. 1967. An electron transport system in mitochondrial outer membrane.J. Cell Biol. 32:415–421
Williams-Ashman, G.H. 1963. Sorbitol dehydrogenase.In: Methods of Enzymatic Analysis. H.U. Bergmeyer, editor. pp. 176–178. Verlag Chemie Academic Press, New York
Wilson, P.W., Lawson, D.E.M. 1980. Calcium binding activity by chick intestinal brush-border membrane vesicles.Pfluegers Arch. 389:64–74
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maenz, D.D., Forsyth, G.W. Ricinoleate and deoxycholate are calcium ionophores in jejunal brush border vesicles. J. Membrain Biol. 70, 125–133 (1982). https://doi.org/10.1007/BF01870222
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01870222