Summary
The characteristics of the inhibitory influence exerted by amiloride on active sodium transport by toad bladder and skin were taken advantage of to shed additional light on the mechanism whereby hormones-chiefly aldosterone-stimulate sodium transport across such epithelia.
Toad skin treated with amiloride was as responsive to vasopressin and to aldosterone as the matched control preparation, while the response of toad skin to insulin was blunted under similar circumstances.
When aldosterone-stimulated toad skin was exposed to amiloride, the resulting depression of sodium-transporting activity was less pronounced than was the case with matched control; on the other hand, insulin-treated membranes were as sensitive to amiloride as matched controls. Similar observations were made with triamterene.
This is taken to indicate that the density of the ‘permeases’ apparently required for sodium to cross the apical cell border of these specialized epithelia, is increased under the influence of aldosterone.
The affinity of amiloride for toad bladder tissue was not influenced by aldosterone, as indicated by tissue labelling experiments.
Similar content being viewed by others
References
Baba, W. I., A. F. Lant, A. J. Smith, M. M. Townshend, andG. M. Wilson: Pharmacological effects in animals and normal human subjects of the diuretic amiloride hydrochloride (MK-870). Clin. Pharmacol. Ther.9, 318–327 (1968).
—,G. R. Tudhope, andG. M. Wilson: Site and mechanism of action of the diuretic, triamterene. Clin. Sci.27, 181–193 (1964).
Baer, J. E., C. B. Jones, S. A. Spitzer, andH. F. Russo: The potassiumsparing and natriuretic activity of N-amidino-3,5-diamino-6-chloropyrazine carboxamide hydrochloride dihydrate (amiloride hydrochloride). J. Pharmacol. exp. Ther.157, 472–485 (1967).
Bentley, P. J.: Amiloride: a potent inhibitor of sodium transport across the toad bladder. J. Physiol. (Lond.)195, 317–330 (1968).
Cereijido, M., F. C. Herrera, W. J. Flanigan, andP. F. Curran: The influence of Na concentration on Na transport across frog skin. J. gen. Physiol.47, 879–893 (1964).
Cofré, G., andJ. Crabbé: Active sodium transport by the colon ofBufo marinus: stimulation by aldosterone and antidiuretic hormone. J. Physiol. (Lond.)188, 177–190 (1967).
Cohen, G. N., andJ. Monod: Bacterial permeases. Bact. Rev.21, 169–194 (1957).
Crabbé, J.: Stimulation of active sodium transport across the isolated toad bladder after injection of aldosterone to the animal. Endocrinology69, 673–682 (1961).
—: Stimulation of active sodium transport by the isolated toad bladder with aldosteronein vitro. J. clin. Invest.40, 2103–2110 (1961).
—: Stimulation by aldosterone of active sodium transport across the isolated ventral skin of amphibia. Endocrinology75, 809–811 (1964).
Crabbé, J.: The mechanism of action of aldosterone. Proc. 3rd int. Congress Endocrinol., Mexico, June 30–July 5, 1968.
—: A hypothesis concerning the mode of action of amiloride and of triamterene. Arch. int. Pharmacodyn. Thér.173, 474–477 (1968).
—, etB. François: Stimulation par l'insuline du transport actif de sodium à travers les membranes épithéliales du crapaud,Bufo marinus. Ann. Endocr. (Paris)28, 713–715 (1967).
Crabbé, J., andJ. Scarlata: Stimulation by insulin of active sodium transport. Proc. 4th ann. Meet. Eur. Ass. for the Study of Diabetes, Leuven, July 22–24, 1968.
—, andP. De Weer: Probable role of a “permease” in sodium transport by some epithelial membranes: influence of aldosterone. Protides biol. Fluids (H. Peeters, Ed.), vol. 15, pp. 213–215. Amsterdam: Elsevier 1968.
Curran, P. F., F. C. Herrera, andW. J. Flanigan: The effect of Ca and antidiuretic hormone on Na transport across frog skin. II. Sites and mechanisms of action. J. gen. Physiol.46, 1011–1027 (1963).
Ehrlich, E. N., andJ. Crabbé: The mechanism of action of amipramizide. Pflügers Arch.302, 79–96 (1968).
Eigler, J., J. Kelter, andE. Renner: Wirkungscharakteristika eines neuen Acylguanidins-Amiloride-HCl (MK-870) an der isolierten Haut von Amphibien. Klin. Wschr.45, 737–738 (1967).
Fanestil, D. D.: Rate limiting step in aldosterone action. Fed. Proc.27, 315 (1968).
Fimognari, G. M., G. A. Porter, andI. S. Edelman: The role of the tricarboxylic acid cycle in the action of aldosterone on sodium transport. Biochim. biophys. Acta (Amst.)135, 89–99 (1967).
Frazier, H. S., E. F. Dempsey, andA. Leaf: Movement of sodium across the mucosal surface of the isolated toad bladder and its modification by vasopressin. J. gen. Physiol.45, 529–543 (1962).
Herrera, F. C.: Effect of insulin on short-circuit current and sodium transport across toad urinary bladder. Amer. J. Physiol.209, 819–824 (1965).
Leaf, A.: Membrane effects of antidiuretic hormone. Amer. J. Med.42, 745–756 (1967).
Lichtenstein, N. S., andA. Leaf: Effect of amphotericin B on the permeability of the toad bladder. J. clin. Invest.44, 1328–1342 (1965).
Porter, G. A., andI. S. Edelman: The action of aldosterone and related corticosteroids on sodium transport across the toad bladder. J. clin. Invest.43, 611–620 (1964).
Schultz, S. G., andR. Zalusky: Ion transport in isolated rabbit ileum. I. Short-circuited current and Na fluxes. J. gen. Physiol.47, 567–584 (1964).
Sharp, G. W. G., C. H. Coggins, N. S. Lichtenstein, andA. Leaf: Evidence for a mucosal effect of aldosterone on sodium transport in the toad bladder. J. clin. Invest.45, 1640–1646 (1966).
Ussing, H. H., andK. Zerahn: Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta physiol. scand.23, 110–127 (1951).
Wiebelhaus, V. D., J. Weinstock, A. R. Mass, F. T. Brennan, G. Sosnowski, andT. Larsen: The diuretic and natriuretic activity of triamterene and several related pteridines in the rat. J. Pharmacol. exp. Ther.149, 397–403 (1965).
Author information
Authors and Affiliations
Additional information
Supported financially by the Fonds de la Recherche Scientifique Médicale (grant no 988), Belgium.
On leave of absence from the University of Chicago, Department of Medicine. Recipient of a U.S.P.H.S. Career Development Award K2-GM21.842.
Rights and permissions
About this article
Cite this article
Crabbé, J., Ehrlich, E.N. & Scarlata, J. Amiloride and the mode of action of aldosterone on sodium transport across toad bladder and skin. Pflugers Arch. 304, 284–296 (1968). https://doi.org/10.1007/BF00592131
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00592131