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Papaverine reduces the sodium permeability of the apical membrane and the Potassium permeability of the basolateral membrane in isolated frog skin

The Journal of Membrane Biology volume 126, pages 235–243 (1992)Cite this article

Summary

The effect of papaverine, an inhibitor of the phosphodiesterase responsible for breakdown of cAMP, on the transepithelial sodium transport across the isolated frog skin was investigated.

Serosal addition of papaverine caused initially an increase in the short-circuit current (SCC), a doubling of the cellular cAMP content and a depolarization of the intracellular potential under SCC conditions (V scc).

The initial increase in the SCC was followed by a pronounced decrease both in the SCC and in the natriferic action of antidiuretic hormone (ADH), but papaverine had no inhibitory effect on the ability of ADH to increase the cellular cAMP content. As SCC declines, no hyperpolarization was observed.

The I/V relationship across the apical membrane during the inhibitory phase, revealed that papaverine reduces the sodium permeability of the apical membrane (P aNa )as well as intracellular sodium concentration. These observations and the previously noted effect of papaverine on V scc indicates that papaverine must have an effect on the cellular Cl or K permeability.

The basolateral Na,K,2Cl cotransporter was blocked with bumetanide, which should bring the cellular chloride in equilibrium. Bumetanide had no effect on basal SCC and V scc. When papaverine was added to skins preincubated with bumetanide, the effect of papaverine on SCC and V scc was unchanged. Therefore, the depolarization of V scc, observed during the papaverine induced inhibition of the SCC, must be due to a reduction in the cellular K permeability.

In conclusion, it is suggested that papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane of the frog skin epithelium.

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References

  • Andersen, H., Nielsen, R. 1989. Effect of calcium and antidiuretic hormone (AVT) on K+ secretion from epithelial cells of isolated frog skin. Proc. Int. Union. Physiol. Sci. 17:147

    Google Scholar 

  • Baba, W., Smith, A., Townshend, M. 1967. The effect of vasopressin, theophylline and 3′-5′-adenosine monophosphate (cAMP) on sodium transport across the frog skin. Quart. J. Exp. Physiol. 52:416–421

    Google Scholar 

  • Bolton, T.B. 1979. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol. Rev. 59:606–718

    Google Scholar 

  • Christensen, O., Zeuthen, T. 1987. Maxi K+ channels in leaky epithelia are regulated by intracellular Ca2+, pH and membrane potential. Pfluegers Arch. 408:249–259

    Google Scholar 

  • Dacquet, C., Mironneau, C., Mironneau, J. 1987. Effects of calcium entry blockers on calcium-dependent contractions of rat portal vein. Br. J. Pharmacol. 39:444–448

    Google Scholar 

  • Els, W.J., Helman, S.I. 1981. Vasopressin, theophylline, PGE2, and indomethacin on active Na transport in frog skin: Studies with microelectrodes. Am. J. Physiol. 241:F279-F288

    Google Scholar 

  • Erlij, D., Gersten, L., Sterba, G. 1981. Calcium, prostaglandine and transepithelial sodium transport. J. Physiol. 320:136P

    Google Scholar 

  • Erlij, D., Smith, M.W. 1973. Sodium uptake by frog skin and its modification by inhibitors of transepithelial sodium transport. J. Physiol. 228:221–239

    Google Scholar 

  • Ferreira, K.T.G., Ferreira, H.G. 1981. The regulation of volume and ion composition in frog skin. Biochim. Biophys. Acta. 646:193–202

    Google Scholar 

  • Geisler, A., Klysner, R., Thams, P., Christensen, S. 1977. A simple and inexpensive protein binding assay for cyclic AMP in biological materials. Acta. Pharmacol. Toxicol. 40:356–368

    Google Scholar 

  • Harvey, B.J., Kernan, R.P. 1984. Sodium-selective microelectrode study of apical permeability in frog skin: Effect of sodium, amiloride and ouabain. J. Physiol. 356:359–374

    Google Scholar 

  • Harvey, B.J., Urbach, V., Van Kerkhove, E. 1991. Inwardrectifier K+ channels in principal cells of isolated frog skin epithelium and in cultured A6 cells. J. Physiol. 438:158P

    Google Scholar 

  • Helman, S.I., Cox, T.C., van Driessche, W. 1983. Hormonal control of apical membrane Na transport in epithelia. J. Gen. Physiol. 82:201–220

    Google Scholar 

  • Helman, S.I., Fisher, R.S. 1977. Microelectrode studies of the active Na+-transport pathway of frog skin. J. Gen. Physiol. 69:571–604

    Google Scholar 

  • Hertle, L., Nawrath, H. 1990. Effects of papaverine on human isolated bladder muscle. Urol. Res. 18:227–231

    Google Scholar 

  • Ito, Y., Itoh, T. 1984. The roles of stored calcium in contractions of cat tracheal smooth muscle produced by electrical stimulation, acetylcholine and high K+. Br. J. Pharmacol. 83:667–676

    Google Scholar 

  • Johnsen, A.H., Nielsen, R. 1982. Enhanced sensitivity to stimulation of sodium transport and cyclic AMP by antidiuretic hormone after Ca2+ depletion of isolated frog skin epithelium. J. Membrane Biol. 69:137–143

    Google Scholar 

  • Johnsen, A.H., Nielsen, R. 1984. Correlation between cAMP in isolated frog skin epithelium and stimulation of sodium transport and osmotic water flow by antidiuretic hormone and phosphodiesterase inhibitors. Gen. Comp. Endocrinol. 54:144–153

    Google Scholar 

  • Klaerke, D.A., Jørgensen, P.L. 1988. Role of Ca2+-activated K+ channel in regulation of NaCl reabsorption in thick ascending limp of Henle's loop. Comp. Biochem, Physiol. 90A:757–765

    Google Scholar 

  • Koefoed-Johnsen, V., Ussing, H.H. 1958. The nature of the frog skin potential. Acta. Physiol. Scand. 42:298–308

    Google Scholar 

  • Kristensen, P., Ussing, H.H. 1985. Epithelial organisation. In: The Kidney, Physiology and Pathophysiology. D.W. Seldin and G. Giebisch, editors, pp. 173–188. Raven Press, New York

    Google Scholar 

  • Larsen, E.H. 1973. Effect of amiloride, cyanide and ouabain on the active transport pathway in toad skin. In: Transport Mechanisms in Epithelia. Vol. 3, pp. 131–147. H.H. Ussing and N.A. Thorn, editors. Muncksgaard, Copenhagen

    Google Scholar 

  • Larsen, E.H. 1988. NaCl transport in amphibian skin. In: NaCl Transport in Epithelia. Vol. 1, pp. 189–248. R. Greger, editor. Springer-Verlag, Berlin

    Google Scholar 

  • Larsen, E.H. 1991. Chloride transport by high resistance heterocellular epithelia. Physiol. Rev. 71:235–283

    Google Scholar 

  • Loo, D.D.F., Kaunitz, J.D. 1989. Ca2+ and cAMP activate K+ channels in the basolateral membrane of crypt cells isolated from rabbit distal colon. J. Membrane Biol. 110:19–28

    Google Scholar 

  • Lugnier, C., Stocklet, J.C. 1974. Inhibition by papaverine of cGMP and cAMP phosphodiesterases from rat heart. Biochem. Pharmacol. 23:3071–3074

    Google Scholar 

  • Miyamoto, M. Takayanagi, L, Ohkubo, H., Takagi, K. 1976. Actions of papaverine on intestinal smooth muscle and its inhibition of cyclic AMP and cyclic GMP phosphodiesterases. Jpn. J. Pharmacol. 26:114–117

    Google Scholar 

  • Nagel, W. 1979. Inhibition of potassium conductance by barium in frog skin epithelium. Biochim. Biophys. Acta. 552:346–357

    Google Scholar 

  • Nagel, W. 1980. The time course of pump inhibition by ouabain in amphibian skin. Biochim. Biophys. Acta. 599:736–740

    Google Scholar 

  • Nielsen, R. 1984. Active transepithelial potassium transport in frog skin via specific potassium channels in the apical membrane. Acta. Physiol. Scand. 120:287–296

    Google Scholar 

  • Nielsen, R. 1985. Ba2+-induced changes in the Na+ and K+permeability of isolated frog skin. Acta. Physiol. Scand. 124:61–70

    Google Scholar 

  • Poch, G., Kukovetz, V.R. 1971. Papaverine-induced inhibition of phosphodiesterase activity in various mammalian tissue. Life. Sci. 10:133–144

    Google Scholar 

  • Rajerison, R.M., Montegut, M., Jard, S., Morel, F. 1972. The isolated frog skin epithelium: Permeability characteristics and responsiveness to oxytocin, cyclic AMP and theophylline. Pfluegers. Arch. 332:302–312

    Google Scholar 

  • Schoen, H.F., Erlij, D. 1985. Current-voltage relations of the apical and basolateral membranes of the frog skin. J. Gen. Physiol. 86:257–287

    Google Scholar 

  • Triner, L., Nahas, G.G., Vulliemoz, Y., Overweg, N.I.A., Verosky, M., Habif, K.V., Ngai, S.H. 1971. Cyclic AMP and smooth muscle function. Ann. NY Acad. Sci. 185:458–463

    Google Scholar 

  • Ussing, H.H. Zerahn, K. 1951. Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta. Physiol. Scand. 23:110–127

    Google Scholar 

  • Villar, A., D'Ocon, M.P., Anselmi, E. 1986. Role of intracellular calcium stores in the contractile response of uterus to several agonists. J. Pharmacol. 17:541–546

    Google Scholar 

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  1. Institute of Biological Chemistry A, University of Copenhagen, Denmark

    Henning Andersen & Robert Nielsen

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  1. Henning Andersen
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  2. Robert Nielsen
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Andersen, H., Nielsen, R. Papaverine reduces the sodium permeability of the apical membrane and the Potassium permeability of the basolateral membrane in isolated frog skin. J. Membarin Biol. 126, 235–243 (1992). https://doi.org/10.1007/BF00232320

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  • DOI: https://doi.org/10.1007/BF00232320

Key Words

  • cAMP
  • cell Na+
  • frog skin
  • Na+ permeability
  • papaverine