Summary
The effect of ethacrynic acid on fluid and electrolyte transport by the guinea pig gallbladder was investigated in vitro. 10−4M ethacrynic acid, applied to the serosal side, inhibited fluid and sodium chloride absorption. The reduction in salt absorption was accounted for by a 3 μEq/cm2h decrease in the unidirectional fluxes of Na and Cl from mucosa to serosa with no change in the fluxes from serosa to mucosa. Ethacrynic acid (10−4 M) had no effect on HCO3−Cl exchange, PGE1-induced fluid secretion and inulin permeability. At 10−3 M, ethacrynic acid markedly increased both the serosa to mucosa fluxes of Na and Cl, and the inulin permeability. Examination by light and electron microscopy of gallbladder tissue treated with 10−3 M ethacrynic acid revealed large intracellular vacuoles and occasionally ruptured apical cell membranes. Only slight morphological changes were seen by 10−4 M ethacrynic acid with no changes in the controls and ouabain treated gallbladders. The effects of ethacrynic acid are remarkably different from those of furosemide which has been previously shown to inhibit only the HCO3 secretion leaving fluid and NaCl absorption unchanged.
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Al-Awqati, Q., Field, M., Greenough, W. B. III: Reversal of cyclic AMP-mediated intestinal secretion by ethacrynic acid. J. Clin. Invest. 53, 687–692 (1974)
Alguire, P. C., Bailie, M. D., Weaver, W. J., Taylor, D. G., Hook, J.-B.: Differential effects of furosemide and ethacrynic acid on electrolyte excretion in anaesthetized dogs. J. Pharmacol. Exp. Ther. 190, 515–522 (1974)
Beyenbach, K. W., Dantzler, W. H.: Generation of transepithelial potentials by isolated perfused reptilian distal tubules. Am. J. Physiol. 234, F238-F246 (1978)
Burg, M., Green, N.: Effect of ethacrynic acid on the thick ascending limb of Henle's loop. Kidney Int. 4, 301–308 (1973)
Burg, M., Stoner, L., Cardinal, J., Green, N.: Furosemide effect on isolated perfused tubules. Am. J. Physiol. 225, 119–124 (1973)
Cassidy, M. M.: Characteristics of the (Na++K+)-stimulated ATPase of rat jejunum. J. Physiol. (Lond.) 210, 153P-154P (1970)
Chez, R. A., Horger, E. O. III, Schultz, S. G.: The effect of ethacrynic acid on sodium transport by isolated rabbit ileum. J. Pharmacol. Exp. Ther. 168, 1–5 (1969)
Diamond, J. M.: The reabsorptive function of the gallbladder. J. Physiol. (Lond.) 161, 442–473 (1962)
Edsal, J. I., Wyman, J.: Biophysical chemistry, Vol. 1. New York: Acad. Press 1958
Frederiksen, O.: Functional distinction between two transport mechanisms in rabbit gallbladder epithelium by use of ouabain, ethacrynic acid and metabolic inhibitors. J. Physiol. (Lond.) 280, 373–388 (1978)
Frizzell, R. A., Heintze, K.: Transport functions of the gallbladder. In: Int. Rev. Physiol., Liver Physiol. (N. B. Javitt, ed.). Baltimore: University Park Press (in press), 1979)
Frizzell, R. A., Dugas, M. C., Schultz, S. G.: Sodium chloride transport by rabbit gallbladder: Direct evidence for a coupled NaCl influx process. J. Gen. Physiol. 65, 769–795 (1975)
Frömter, E., Geßner, K.: Effect of inhibitors and diuretics on electrical potential differences in rat kidney proximal tubule. Pflügers Arch. 357, 209–224 (1975)
Heintze, K.: Prostaglandine und Elektrolyttransport: Eine Flüssigkeitsresorption wird in eine Sekretion überführt. Fortschr. Med. 95, 1463–1466 (1977)
Heintze, K., Manjura, K.: Effect of some diuretics on the Na+, K+-stimulated, Mg2+-dependent adenosine triphosphatase activity from the intestine of guinea pigs. Proc. 6th. Int. Congress Pharmacology, Helsinki 1975, R 865
Heintze, K., Götz, R., Koerlings, H., Wood, J. R.: Characterization of the prostaglandin-induced secretion in the isolated gallbladder of guinea pig. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, R34 (1976)
Heintze, K., Petersen, K.-U., Busch, L. C.: Effects of hydrostatic pressure on fluid transfer by the isolated gallbladder. Pflügers Arch. 373, 9–13 (1978)
Heintze, K., Petersen, K.-U., Olles, P., Saverymuttu, S. H., Wood, J. R.: Effects of bicarbonate on fluid and electrolyte transport by the guinea pig gallbladder: A bicarbonate-chloride exchange. J. Membr. Biol. 45, 43–59 (1979)
Matuchansky, C., Mary, J. Y., Bernier, J. J.: Further studies on prostaglandin E1-induced jejunal secretion of water and electrolytes in man, with special reference to the influence of ethacrynic acid, furosemide and aspirin. Gastroenterology 71, 274–281 (1976)
Schwartz, A., Lindenmayer, G. E., Allen, J. C.: The sodiumpotassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects. Pharmacol. Rev. 27, 3–134 (1975)
Smulders, A. P., Wright, E. M.: The magnitude of non-electrolyte selectivity in the gallbladder epithelium. J. Membr. Biol. 5, 297–318 (1971)
van Os, C. H., Slegers, J. F. G.: Characteristics of Na+−K+-stimulated ATPase in rabbit gallbladder epithelium. Pflügers Arch. 319, 49–56 (1970)
van Rossum, G. D. V., Ernst, S. A.: Effects of ethacrynic acid on ion transport and energy metabolism in slices of avian salt gland and of mammalian liver and kidney cortex. J. Membr. Biol. 43, 251–275 (1978)
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This work was supported by a grant from the Deutsche Forschungsgemeinschaft given to the Sonderforschungsbereich 160. “Eigenschaften biologischer Membranen”, Projekt C2
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Petersen, KU., Heintze, K., Busch, L.C. et al. Effects of ethacrynic acid on electrolyte and fluid transport by the guinea pig gallbladder. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 287–294 (1979). https://doi.org/10.1007/BF00504762
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DOI: https://doi.org/10.1007/BF00504762