The Sigma-1 Receptor Ligands Chlorpromazine and Trifluoperazine Inhibit Na+ Transport in Frog Skin Epithelium


Using the voltage-clamp technique, it has been shown for the first time that the neuroleptic drugs chlorpromazine and trifluoperazine, which act as sigma-1 receptor antagonists, attenuate Na+ transport in the frog skin epithelium. The results suggest that sigma-1 receptors may be involved in the regulation of transepithelial Na+ transport in frog skin.

This is a preview of subscription content, access via your institution.

Fig. 1.


  1. 1

    Yu. V. Natochin, Fundamentals of Renal Physiology (Nauka, Leningrad, 1982) [in Russian].

    Google Scholar 

  2. 2

    S. Kellenberger and L. Schild, Physiol. Rev. 82, 735 (2002).

    Article  Google Scholar 

  3. 3

    C. G. Rousseaux and S. F. Greene, J. Recept. Signal. Trans. 36, 327 (2016).

    Google Scholar 

  4. 4

    S. B. Hellewell, A. Bruce, G. Feinstein, et al., Eur. J. Pharmacol. 268, 9 (1994).

    Article  Google Scholar 

  5. 5

    E. J. Cobos, J. M. Entrena, F. R. Nieto, et al., Curr. Neuropharmacol. 6, 344 (2008).

    Article  Google Scholar 

  6. 6

    Y. Itzhak, M. Ruhland, and H. Krahling, Neuropharmacology 29, 181 (1990).

    Article  Google Scholar 

  7. 7

    B. Penke, L. Fulop, M. Szucs, et al., Curr. Neuropharmacol. 16, 97 (2018).

    Google Scholar 

  8. 8

    T.-P. Su, T. Hayashi, T. Maurice, et al., Trends Pharmacol. Sci. 31, 557 (2010).

    Article  Google Scholar 

  9. 9

    S. M. Carnally, M. Johannessen, R. M. Henderson, et al., Biophys. J. 98, 1182 (2010).

    Article  ADS  Google Scholar 

  10. 10

    Z. I. Krutetskaya, O. E. Lebedev, A. V. Melnitskaya, et al., Dokl. Akad. Nauk 421 (5), 709 (2008).

    Google Scholar 

  11. 11

    R. W. Van Dyke and B. F. Scharschmidt, Am. J. Physio-l. 253, 613 (1987).

    Article  Google Scholar 

  12. 12

    P. Else and K. Mansfield, Biochem. Pharmacol. 54, 275 (1997).

    Article  Google Scholar 

  13. 13

    M. S. Awayda, W. Shao, F. Guo, et al., J. Gen. Physiol. 123, 709 (2004).

    Article  Google Scholar 

  14. 14

    S. D. Levine, W. A. Kachadorian, D. N. Levin, et al., J. Clin. Invest. 67 (3), 662 (1981).

    Article  Google Scholar 

  15. 15

    H. F. Bjerregaard and R. Nielsen, Acta Physiol. Scand. 127 (1), 75 (1986).

    Article  Google Scholar 

  16. 16

    H. F. Bjerregaard and R. Nielsen, Acta Physiol. Scand. 134 (1), 43 (1988).

    Article  Google Scholar 

  17. 17

    M. D. Feldkamp, S. E. O’Donnell, L. Yu, et al., Proteins 78 (10), 2265 (2010).

    Article  Google Scholar 

  18. 18

    Y. Herrera, C. Katnik, J. D. Rodriguez, et al., J. Pharmacol. Exp. Ther. 327, 491 (2008).

    Article  Google Scholar 

  19. 19

    A. V. Melnitskaya, Z. I. Krutetskaya, S. N. Butov, et al., in Receptors and Intracellular Signaling, Ed. by V. P. Zin-chenko and A. V. Berezhnov (Fix-Print, Pushchino, 2017), pp. 55–58.

Download references


This study was conducted as a part of the research program of the Department of Biophysics of St. Petersburg State University and the Department of Clinical Bioche-mistry and Laboratory Diagnostics of the Kirov Military Medical Academy (St. Petersburg) and was supported by Research and Development Agreement no. 28-12-38.

Author information



Corresponding authors

Correspondence to A. V. Melnitskaya or Z. I. Krutetskaya.

Ethics declarations

Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and institutional guidelines for the care and use of animals were followed.

Additional information

Translated by D. Timchenko

Abbreviations: ENaC—amiloride-sensitive epithelial sodium channel; Deg/ENaC—degenerin/epithelial sodium channel superfamily; ASICs—acid-sensing ion channels; CP—chlorpromazine; TFP—trifluoperazine.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Melnitskaya, A.V., Krutetskaya, Z.I., Antonov, V.G. et al. The Sigma-1 Receptor Ligands Chlorpromazine and Trifluoperazine Inhibit Na+ Transport in Frog Skin Epithelium. BIOPHYSICS 65, 784–787 (2020).

Download citation

  • Keywords: sigma-1 receptors
  • Na+ transport
  • chlorpromazine
  • trifluoperazine