Summary
Amphibian epithelia have been used as models for studying the effects of psychotropic drugs on membrane transport. Several of these agents added to the internal or to the external media, at concentrations greater than 10−3 m, had inhibitory, “ouabainlike” effects on Na transport. In contrast, stimulatory, “vasopressin-like” effects were seen at lower concentrations. The stimulation was additive to that of oxytocin if the drug was present in the external solution but nonadditive if in the internal solution. On water transport, harmala alkaloids had a vasopressinomimetic action in toad skin, while inhibition was seen with Li and amitriptyline. To account for these multiple effects, it is hypothesized that psychotropic drugs act on the following cell targets: the Na pump, the cyclic nucleotide system, microtubules, and membrane calcium sites at the outer barrier of the epithelium. Direct, biochemical evidence is needed to substantiate this hypothesis.
Similar content being viewed by others
References
Berridge, M.J., Prince, W.T. 1974. The nature of the binding between LSD and a 5-HT receptor: A possible explanation for hallucinogenic activity.Br. J. Pharmacol. 51:269
Bhattacharyya, B., Wolff, J. 1976. Stabilization of microtubules by lithium ion.Biochem. Biophys. Res. Commun. 73:383
Butcher, R.W., Sutherland, E.W. 1962. Adenosine 3′,5′-phosphate in biological materials. I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′,5′-phosphate in human urine.J. Biol. Chem. 237:1244
Canessa, M., Jaimovich, E., Fuente, M. de la. 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
Cox, M., Singer, I. 1975. Lithium and water metabolism.Am. J. Med. 59:153
Crabbé, J., Khatcheressian, I. 1976. Disappearance of insulin response after enzymatic treatment of sodium-transporting amphibian epithelia.Pfluegers Arch. 364:99
Dean, R.B. 1941. Theories of electrolyte equilibrium in muscle.Biol. Symp. 3:331
De Sousa, R.C. 1975. Mécanismes de transport de l'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 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
DeSousa, R.C., Grosso, A. 1978. Vasopressin-like effects of a hallucinogenic drug—harmaline—on sodium and water transport.J. Membrane Biol. 40:77
De Sousa, R.C., Grosso, A., Rufener, C. 1974. Blockade of the hydrosmotic effect of vasopressin by cytochalasin B.Experientia 30:175
Ehrenfeld, J., Garcia-Romeu, F. 1977. Effect of harmaline on sodium transport inRana esculenta skin.Br. J. Pharmacol. 59:115
Forrest, J.N., Jr., Cohen, A.D., Torretti, J., Himmelhoch, J.M., Epstein, F.H. 1974. On the mechanism of lithium-induced diabetes insipidus in man and the rat.J. Clin. Invest. 53:1115
Graziani, Y., Chayoth, R. 1977. Elevation of cyclic AMP level in Ehrlich ascites tumor cells by quercetin.Biochem. Pharmacol. 26:1259
Grin, J., Bueno, E.J. 1973. Effect of cocaine on Na channel in toad skin.Can. J. Physiol. Pharmacol. 51:516
Grosso, A., De Sousa, R.C. 1977. Vasopressin-like effects of harmaline on water transport: interaction with lithium and potassium. XXVIIth International Congress of Physiological Sciences, Paris, 1977. (Abstr.) p. 288
Grundy, H.F. 1966. The effects of morphine, pethidine and nalorphine on the isolated frog skin preparation.J. Pharm. Pharmacol. 18:694
Harris, R.A., Iwamoto, E.T., Loh, H.H., Way, E.L. 1975. Analgetic effects of lanthanum: cross-tolerance with morphine.Brain Res. 100:221
Harrisson, C.M.H., Page, B.M., Keir, H.M. 1976. Mescaline as a mitotic spindle inhibitor.Nature (London) 260:138
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
Hinman, N.D., Cann, J.R. 1976. Reversible binding of chlorpromazine to brain tubulin.Mol. Pharmacol. 12:769
Huang, M., Daly, J.W. 1972. Accumulation of cyclic adenosine monophosphate in incubated slices of brain tissue. 1. Structure-activity relationships of agonists and antagonists of biogenic amines and of tricyclic tranquilizers and antidepressants.J. Med Chem. 15:458
Kwant, W.O., Seeman, P. 1969. The displacement of membrane calcium by a local anesthetic (chlorpromazine).Biochim. Biophys. Acta 193:338
Lampert, A., Nirenberg, M., Klee, W.A. 1976. Tolerance and dependence evoked by an endogenous opiate peptide.Proc. Nat. Acad. Sci. USA 73:3165
Lelievre, L., Paraf, A., Charlemagne, D., Sheppard, J.R. 1977. Plasma membrane studies on drug sensitive and resistant cell lines. Exp. Cell Res.104:191
Levine, S.D., Franki, N., Einhorn, R., Hays, R.M. 1976. Vasopressin-stimulated movement of drugs and uric acid across the toad uninary bladder.Kidney Int. 9:30
Mamelak, M., Weissbluth, M., Maffly, R.H. 1970. Effect of chlorpromazine on permeability of the toad bladder.Biochem. Pharmacol. 19:2303
Marguerat, J.D. 1975. Lanthanides et épithéliums 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
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
McClane, T.K. 1965. A biphasic action of ouabain on sodium transport in the toad bladder.J. Pharmacol. Exp. Ther. 148:106
Medzihradsky, F., Nandhasri, P.S. 1972. Effects of some analgesics and antidepressants on the (Na++K+)-adenosine triphosphatase from cortices of brain and kidney.Biochem. Pharmacol. 21:2103
Mikkelsen, R.B. 1976. Lanthanides as calcium probes in biomembranes.In: Biological Membranes. Vol. 3, p. 153. D. Chapman and D.F.H. Wallach, editors. Academic Press, New York
Mózsik, G. 1969. Some feed-back mechanisms by drugs in the interrelationship between the active transport system and adenyl cyclase system localized in the cell membrane.Eur. J. Pharmacol. 7:319
Nathanson, J.A. 1977. Cyclic nucleotides and nervous system function.Physiol. Rev. 57:157
Nathanson, J.A., Greengard, P. 1974. Serotonin-sensitive adenylate cyclase in neural tissue and its similarity to the serotonin receptor: A possible site of action of lysergic acid diethylamide.Proc. Nat. Acad. Sci. USA 71:797
Palatini, P. 1977. Mechanism of inhibition of sodium- and potassium-dependent adenosine triphosphatase by tricyclic antipsychotics.Mol. Pharmacol. 13:216
Pietras, R.J., Naujokaitis, P.J., Szego, C.M. 1976. Differential effects of vasopressin on the water, calcium and lysosomal enzyme contents of mitochondria-rich and lsysosome-rich (granular) epithelial cells isolated from bullfrog urinary bladder.Mol. Cell. Endocrinol. 4:89
Poffenbarger, M., Fuller, G.M. 1977. Effects of psychotropic drugs on neurotubule assembly.J. Neurochem. 28:1167
Robinson, J.D. 1975. Harmaline inhibits the (Na++K+)-dependent ATPase by affecting both Na+ and K+ activation.Biochem. Pharmacol. 24:2005
Roufogalis, B.D. 1975. Comparative studies on the membrane actions of depressant drugs: The role of lipophilicity in inhibition of brain sodium and potassium-stimulated ATPase.J. Neurochem. 24:51
Rüphi, M., Sousa, R.C. de, Favrod-Coune, E., Posternak, J.M. 1972. Optical method for measuring water flow with automatic recording.Experientia 28:1391
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
Sharma, S.K., Klee, W.A., Nirenberg, M. 1975. Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance.Proc. Natl. Acad. Sci. USA 72:3092
Sharma, S.K., Klee, W.A., Nirenberg, M. 1977. Opiate-dependent modulation of adenylate cyclase.Proc. Nat. Acad. Sci. USA 74:3365
Skou, J.C. 1957. The influence of some cations on an adenosine triphosphatase from peripheral nerves.Biochim. Biophys. Acta. 23:394
Sutherland, E.W., Rall, T.W., Menon, T. 1962. Adenyl cyclase. I. Distribution, preparation and properties.J. Biol. Chem. 237:1220
Taylor, A. 1977. Role of microtubules and microfilaments in the action of vasopressin.In: Disturbances in Body Fluid Osmolality. Thomas, E. Andreoli, Jared J. Grantham, and Floyd C. Rector, Jr., editors. p. 97. American Physiological Society, Bethesda
Ussing, H.H., Erlij, D., Lassen, U. 1974. Transport pathways in biological membranes.Annu. Rev. Physiol. 36:17
Uzunov, P., Weiss, B. 1972. Psychopharmacological agents and the cyclic AMP system of rat brain.Adv. Cyclic Nucleotide Res. 1:435
Wilson, T.H., Maloney, P.C. 1976. Speculations on the evolution of ion transport mechanisms.Fed. Proc. 35:2174
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grosso, A., de Sousa, R.C. Vasopressin-like effects of psychotropic drugs in amphibian epithelia. J. Membrain Biol. 40 (Suppl 1), 305–321 (1978). https://doi.org/10.1007/BF02026013
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02026013