Abstract
The reversible inhibition of transepithelial sodium transport achieved with amiloride (and triamterene) was evaluated in amphibian preparations stimulated with aldosterone so as to provide further information regarding a possible influence of this hormone on the apical border of target cells.
When aldosterone secretion was enhanced by withdrawal of sodium from toad (Bufo marinus) habitat, sensitivity of abdominal skin to amiloride decreased; the same occurred in skin and bladder preparations incubated with aldosterone for several hours.
Amiloride proved a less efficient blocker of sodium transport by toad skin exposed to vasopressin and to ouabain; both substances are capable or raising cell sodium content. It is therefore proposed that the decrease in sensitivity to amiloride of amphibian epithelia treated with aldosterone results from an increase in target cell sodium, itself due to a hormone-induced increase in sodium conductance at the apical cell border.
Glucose, which enhanced markedly the rate of sodium transport in preparations treated with aldosterone for several hours, failed to decrease any further the response to amiloride; this is taken as an argument for an additional (? secondary) influence of aldosterone on the cell's metabolic machinery connected with the operation of the sodium ‘pump’.
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References
André, R., Crabbé, J.: Stimulation by insulin of active sodium transport by toad skin: Influence of aldosterone and vasopressin. Arch. Int. Physiol. Biochim.73, 538–540 (1966)
Baba, W. I., Lant, A. F., Smith, A. J., Townshend, M. M., Wilson, G. M.: Pharmacological effects in animals and normal human subjects of diuretic amiloride hydrochloride (MK-870). Clin. Pharmacol. Ther.9, 318–327 (1968)
Benjamin, W. B., Singer, I.: Aldosterone-induced protein in toad urinary bladder. Science186, 269–271 (1974)
Benos, D. J., Mandel, L. J.: Amiloride is a non-competitive inhibitor of Na-transport in isolated bullfrog skin. Biophys. J.21, 169A (1978)
Bentley, P. J.: Amiloride: A potent inhibitor of sodium transport across the toad bladder. J. Physiol. (Lond.)195, 317–330 (1968)
Biber, T. U. L.: Effect of changes in transepithelial transport on the uptake of sodium across the outer surface of the frog skin. J. Gen. Physiol.58, 131–144 (1971)
Cereijido, M., Herrera, F. C., Flanigan, W. J., Curran, P. F.: The influence of Na concentration on Na transport across frog skin. J. Gen. Physiol.47, 879–893 (1964)
Crabbé, J.: Stimulation of active sodium transport across the isolated toad bladder after injection of aldosterone to the animal. Endocrinology69, 673–682 (1961)
Crabbé, J.: A hypothesis concerning the mode of action of amiloride and of triamterene. Arch. Int. Pharmacodyn. Thér.173, 474–477 (1968)
Crabbé, J.: Hormonal influences on transepithelial sodium transport: Aldosterone vs insulin. J. Steroid Biochem.3, 229–235 (1972)
Crabbé, J.: Mechanism of action of aldosterone. Ch. 10. In: Part II of ‘receptors and mechanism of action of steroid hormones’, modern pharmacology-toxicology series, Vol. 8 (J. Pasqualini, ed.), pp. 513–568. New York: Marcel Dekker Inc. 1977
Crabbé, J.: Does aldosterone modify the response of target tissues to amiloride? In: Merck symposium on amiloride (A. W. Cuthbert, G. M. Fanelli, Jr, A. Scriabine, eds.), pp. 91–99. Baltimore: Urban & Schwarzenberg 1979
Crabbé, J., Decoene, A., Ehrlich, E. N.: Some characteristics of the response of the ventral skin of the toadBufo marinus, to aldosterone in vitro. Arch. Int. Physiol. Biochim.79, 805–808 (1971)
Crabbé, J., Fanestil, D. D., Pelletier, M., Porter, G. A.: Effect of ouabain on sodium transport across hormone-stimulated toad bladder and skin. Pflügers Arch.347, 275–296 (1974)
Cuthbert, A. W.: An upper limit to the number of sodium channels in frog skin epithelium. J. Physiol. (Lond.)228, 681–692 (1973)
Cuthbert, A. W., Shum, W. K.: Binding of amiloride to sodium channels in frog skin. Mol. Pharmacol.10, 880–891 (1974a)
Cuthbert, A. W., Shum, W. K.: Amiloride and the sodium channel. Naunyn-Schmiedeberg's Arch. Pharmacol.281, 261–269 (1974b)
Cuthbert, A. W., Shum, W. K.: Effects of vasopressin and aldosterone on amiloride binding in toad bladder epithelial cells. Proc. R. Soc. Lond. (Biol.)189, 543–575 (1975)
Cuthbert, A. W., Shum, W. K.: Estimation of the lifespan of amiloride binding sites in the membranes of toad bladder epithelial cells. J. Physiol. (Lond.)255, 605–618 (1976)
Cuthbert, A. W., Shum, W. K.: Does intracellular sodium modify membrane permeability to sodium ions? Nature266, 468–469 (1977)
Cuthbert, A. W., Okpako, D., Shum, W. K.: Aldosterone, moulting and the number of sodium channels in frog skin. Br. J. Pharmacol.51, 128–129 (1974)
De Weer, P., Crabbé, J.: Le mode d'action de l'aldostérone. J. Physiol. (Paris)57, 600–601 (1965)
Dittert, L. W., Higuchi, T., Reese, D. R.: Phase solubility technique in studying the formation of complex salts of triamterene. J. Pharm. Sci.53, 1325–1328 (1964)
Ehrlich, E. N., Crabbé, J.: The mechanism of action of amipramizide. Pflügers Arch.302, 79–96 (1968)
Eigler, J.: Der Einfluß von Aldosteron auf Natriumtransport und transepithelialen Wasserfluß durch isolierte Bauchhaut vonRana temporaria. Pflügers Arch.317, 236–251 (1970)
Frazier, H. S., Dempsey, E. F., Leaf, A.: Movement of sodium across the mucosal surface of the isolated toad bladder and its modification by vasopressin. J. Gen. Physiol.45, 529–543 (1962)
Fuchs, W., Hviid Larsen, E., Lindemann, B.: Current-voltage curve of sodium channels and concentration dependence of sodium permeability in frog skin. J. Physiol. (Lond.)267, 137–166 (1977)
Gatzy, J. T.: Drug interactions of excised toad bladder exposed to low mucosal pH. Pharmacologist13, no 2, Fall 1971
Hviid Larsen, E.: Characteristics of aldosterone stimulated transport in isolated skin of the toadBufo Bufo (L.). J. Steroid Biochem.3, 111–120 (1972)
Koefoed-Johnsen, V., Ussing, H. H.: The nature of the frog skin potential. Acta Physiol. Scand.42, 298–308 (1958)
Kusch, M., Farman, N., Edelman, I. S.: Binding of aldosterone to cytoplasmic and nuclear receptors of the urinary bladder epithelium ofBufo marinus. Am. J. Physiol.235, 682–689 (1978)
Leaf, A.: Membrane effects of antidiuretic hormone. Am. J. Med.42, 745–756 (1967)
Leblanc, G., Morel, F.: Na and K movements across the membranes of frog skin epithelia associated with transient current changes. Pflügers Arch.358, 159–177 (1975)
Moore, R. D.: Effect of insulin upon the sodium pump in frog skeletal muscle. J. Physiol. (Lond.)232, 23–45 (1973)
Nagel, W., Moshagen, B.: Wash out characteristics of tracer Na from the transport pool of frog skin. Pflügers Arch.374, 235–241 (1978)
Nielsen, R., Tomlinson, R. W. S.: The effect of amiloride on sodium transport in the normal and moulting frog skin. Acta Physiol. Scand.79, 238–243 (1970)
Porter, G. A., Edelman, I. S.: The action of aldosterone and related corticosteroids on sodium transport across the toad bladder. J. Clin. Invest.43, 611–620 (1964)
Rick, R., Dörge, A., von Arnim, E., Thurau, K.: Electron microprobe analysis of frog skin epithelium: Evidence of a syncytial sodium transport compartment. J. Membr. Biol.39, 313–331 (1978)
Robbie, D. R.: Studies on the mode of action of aldosterone: The induction hypothesis. Ph. D. Thesis in Physiology, Harvard, U. USA, July 1971
Roloff, C., Dörge, A., Rick, R., Thurau, K.: Effect of vasopressin on intracellular electrolyte composition of the frog skin. Pflügers Arch.377 (Suppl.) R40 (1978)
Rossier, B. D.: Physiological expression of adrenal steroid hormone induction of RNA synthesis. Exc. Med. Int. Congr. Ser. 402. Proc. V. Intern. Congr. End., Hamburg, Vol. 1 (V. H. T. James, ed.), pp. 530–535. Amsterdam: Exc. Med. 1977
Salako, L. A., Smith, A. J.: Changes in sodium pool and kinetics of sodium transport in frog skin produced by amiloride. Br. J. Pharmacol.39, 99–109 (1970)
Scott, W. N., Sapirstein, V. S.: Identification of aldosterone-induced proteins in the toad's urinary bladder. Proc. Natl. Acad. Sci. USA72, 4056–4060 (1975)
Snedecor, G. W.: ‘Statistical Methods’, Iowa State Univ. Press, 5th ed. (1956)
Sudou, K., Hoshi, T.: Mode of action of amiloride in toad urinary bladder. An electrophysiological study of the drug action on sodium permeability of the mucosal border. J. Membr. Biol.32, 115–132 (1977)
Turnheim, K., Frizzell, R. A., Schultz, S. G.: Negative feedback between cell Na and the amiloride-sensitive entry step in rabbit colon. Physiologist20, 96 (1977)
Ulick, S., Feinholtz, E.: Metabolism and rate of secretion of aldosterone in the bullfrog. J. Clin. Invest.47, 2523–2529 (1968)
Ussing, H. H., Zerahn, K.: Active transport of sodium as the source of electric-current in the short-circuited isolated frog skin. Acta Physiol. Scand.23, 110–127 (1951)
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Crabbé, J. Decreased sensitivity to amiloride of amphibian epithelia treated with aldosterone. Pflugers Arch. 383, 151–158 (1980). https://doi.org/10.1007/BF00581876
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DOI: https://doi.org/10.1007/BF00581876