Summary
To determine if harmala alkaloids affect transport systems other than (Na +K)-ATPase, effects of harmaline on Na and water fluxes were studied in amphibian skins. Net Na flux was evaluated from short-circuit current, and water flux monitored with automatic, volumetric methods. At 2 to 5mm, harmaline consistently inhibited SCC and prevented the natriferic effects of oxytocin and norepinephrine. However, at 0.1 to 0.5mm, harmaline produced an increase in SCC inhibitable with amiloride. The stimulatory effects of harmaline and oxytocin were either nonadditive or additive depending on whether the hallucinogen was present in the inner solution or in the outer solution bathing the skin, respectively. Water flow was not modified by harmaline on the outer medium. In contrast, addition of the drug to the inner medium elicited a conspicuous, sustained, vasopressin-like, hydrosmotic effect, comparable to and competitive with those of vasopressin and norepinephrine. The ensemble of these results suggests that harmaline may affect three distinct transport systems: (i) the Na pump; (ii) the cyclic nucleotide system; (iii) the Na entry pathway at the outer membrane of the skin that is also activated by agents such as diphenylhydantoin, lanthanides and propranolol.
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Bastide, F., Jard, S. 1968. Actions de la noradrénaline et de l'ocytocine sur le transport actif de sodium et la perméabilité à l'eau de la peau de grenouille. Rôle du 3′, 5′-AMP cyclique.Biochim. Biophys. Acta 150: 113
Canessa, M., Jaimovich, E., de la Fuente, M. 1972. The effect of harmane derivatives on the Na-dependent phosphorylation from the membrane ATPase system. p. 28. Vth International Congress of Nephrology, Mexico City
Canessa, M., Jaimovich, E., de la Fuente, M. 1973. Harmaline: A competitive inhibitor of Na ion in the (Na++K+)-ATPase system.J. Membrane Biol. 13: 263
Charnock, J.S., Bashford, C.L., Ellory, J.C. 1976. Effects of ATP and magnesium ions on the fluorescence of harmala alkaloids. Restrictions for the use of harmala alkaloids as fluorescent probes for (Na++K+)-ATPase.Biochim. Biophys. Acta 436: 413
Curran, P.F., Gill, J.R., Jr. 1962. The effect of calcium on sodium transport by frog skin.J. Gen. Physiol. 45: 625
Curran, P.F., Herrera, F.C., Flanigan, W.J. 1963. The effect of Ca and antidiuretic hormone on Na transport across frog skin. II. Sites and mechanisms of action.J. Gen. Physiol. 46: 1011
De Sousa, R.C. 1975. Mécanismes de transport d'eau et du sodium par les cellules des épithélia d'amphibiens et du tubule rénal isolé.J. Physiol. (Paris) 71: 5A
De Sousa, R.C. 1976. Effects of a hallucinogenic drug-harmaline-on sodium and water transport.Fed. Proc. 35: 703
De Sousa, R.C. 1976. Effects of amitriptyline and harmaline on sodium and water transport.Experientia,32: 762
De Sousa, R.C., Grosso, A. 1973. Effects of diphenylhydantoin on transport processes in frog skin (Rana ridibunda).Experientia 29: 1097
De Sousa, R.C., Grosso, A., Rufener, C. 1974. Blockade of the hydrosmotic effect of vasopressin by cytochalasin B.Experientia 30: 175
Dunn, M.J., Hunt, W. 1975. The effects of harmaline on sodium transport in human erythrocytes: Evidence in favor of action at interior sodium-sensitive sites.J. Pharmacol. Exp. Ther. 193: 903
Ehrenfeld, J., Garcia-Romeu, F. 1975. Action de l'harmaline sur le transport de sodium à travers la peau isolée deRana esculenta et la branchie d'Astacus leptodactylus.C.R. Acad. Sci. 281: 547
Ehrenfeld, J., Garcia-Romeu, F. 1977. Effect of harmaline on sodium transport inRana esculenta skin.Br. J. Pharmacol. 59: 115
Herrera, F.C., Curran, P.F. 1963. The effect of Ca and antidiuretic hormone on Na transport across frog skin. I. Examination of interrelationships between Ca and hormone.J. Gen. Physiol. 46: 999
Leaf, A. 1965. Transepithelial transport and its hormonal control in toad bladder.Ergeb. Physiol. 56: 216
Levine, S.D., Franki, N., Einhorn, R., Hays, R.M. 1976. Vasopressin-stimulated movement of drugs and uric acid across the toad urinary bladder.Kidney Int. 9: 30
Marguerat, J. 1975. Lanthanides et epitheliums d'amphibiens: Etude des effets sur les transports d'eau et de sodium et de l'interaction avec le couplage stimulus-effet hormonal. Thèse. Université de Genève
Marguerat, J., De Sousa, R.C. 1975. Lanthanides and amphibian epithelia: Block of the hormone-induced stimulation of sodium and water transport.Experientia 31: 73
Martinez-Palomo, A., Erlij, D., Bracho, H. 1971. Localization of permeability barriers in the frog skin epithelium.J. Cell Biol. 50: 277
Marumo, F., Mishina, T., Asano, Y., Tashima, Y. 1976. The inhibitory effect of reserpine on the active sodium transport across the frog bladder.Pfluegers Arch. 365: 15
Porzig, H. 1975. Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts.J. Physiol. 249: 27
Riddle, T.G., Mandel, L.J., Goldner, M.M. 1975. Dilantin-calcium interaction and active Na transport in frog skin.Eur. J. Pharmacol. 33: 189
Robinson, J.D. 1975. Harmaline inhibits the (Na++K+)-dependent ATPase by affecting both Na+ and K+ activation.Biochem. Pharmacol. 24: 2005
Rüphi, M., De Sousa, R.C., Favrod-Coune, E., Posternak, J.M. 1972. Optical method for measuring water flow with automatic recording.Experientia 28: 1391
Samaržija, I., Kinne-Saffran, E., Baumann, K., Frömter, E. 1977. The mechanism of action of harmaline on renal solute transport.Pfluegers Arch. 368: 83
Schwartz, A., Lindenmayer, G.E., Allen, J.C. 1975. The sodium-potassium adenosine triphosphatase: Pharmacological, physiological and biochemical aspects.Pharmacol. Rev. 27: 3
Seeman, P. 1972. The membrane actions of anesthetics and tranquilizers.Pharmacol. Rev. 24: 583
Sepúlveda, F.V., Buclon, M., Robinson, J.W.L. 1976. Differential effects of harmaline and ouabain on intestinal sodium, phenylalanine and β-methyl-glucoside transport.Naunyn-Schmiedeberg's Arch. Pharmakol. 295: 231
Sepúlveda, F.V., Buclon, M., Robinson, J.W.L. 1977. L'harmaline, un inhibiteur des processus de transport intestinal associés aux mouvements des ions sodium.Gastroenterol. Clin. Biol. 1: 87
Sepúlveda, F.V., Robinson, J.W.L. 1974. Harmaline, a potent inhibitor of sodiumdependent transport.Biochim. Biophys. Acta 373: 527
Sepúlveda, F.V., Robinson, J.W.L. 1975. New characteristics of harmaline inhibition of intestinal transport systems.Naunyn-Schmiedeberg's Arch. Pharmacol. 291: 201
Sepúlveda, F.V., Robinson, J.W.L. 1976. The influence of harmaline on sodium and sodium-dependent transport mechanisms.In: Intestinal Ion Transport. J.W.L. Robinson, editor. p. 157. Medical and Technical Publications, Lancaster
Singer, S.J., Nicolson, G.L. 1972. The fluid mosaic model of the structure of cell membrane.Science 175: 720
Ussing, H.H., Erlij, D., Lassen, U. 1974. Transport pathways in biological membranes.Annu. Rev. Physiol. 36: 17
Watson, E.L., Woodbury, D.M. 1972. Effects of diphenylhydantoin on active sodium transport in frog skin.J. Pharmacol. Exp. Ther. 180: 767
Weiss, G.B. 1974. Cellular pharmacology of lanthanum.Annu. Rev. Pharmacol. 14: 343
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de Sousa, R.C., Grosso, A. Vasopressin-like effects of a hallucinogenic drug-harmaline-on sodium and water transport. J. Membrain Biol. 40, 77–94 (1978). https://doi.org/10.1007/BF01909740
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DOI: https://doi.org/10.1007/BF01909740