Using voltage-clamp technique, the influence of two structurally different neuroleptics haloperidol and chlorpromazine on Na+ transport in frog skin was investigated. It was shown for the first time that haloperidol and chlorpromazine modulate the transepithelial Na+ transport. The results obtained also suggest that the regulatory effect of these antipsychotic agents on Na+ transport in frog skin is mediated by distinct signaling mechanisms.
frog skin, transepithelial Na+ transport, haloperidol, chlorpromazine
1. Natochin Yu.V. Osnovy fiziologii pochki. L.: Nauka, 1982, 184 s. [Natochin, Yu.V. Fundamentals of kidney physiology. Leningrad: Nauka, 1982, 184 p. (In Russ.)]
2. Oruch R., Lund A., Pryme I.F., Holmsen H. An intercalation mechanism as a mode of action exerted by psychotropic drugs: results of altered phospholipid substrate availabilities in membranes? J. Chem. Biol., 2010, vol. 3, pp. 67-88.
3. Dilsaver S.C. Antipsychotic agents: a review. Am. Fam. Phys., 1993, vol. 47, pp. 199-204.
4. Van Dyke R.W., Scharschmidt B.F. Effects of chlorpromazine on Na+-K+-ATPase pumping and solute transport in rat hepatocytes. Am. J. Physiol., 1987, vol. 253, pp. 613-621.
5. Else P., Mansfield K. Activiation of sodium transport and intracellular sodium lowering by the neuroleptic drug chlorpromazine. Biochem. Pharmacol., 1997, vol. 54, pp. 275-281.
6. Awayda M.S., Shao W., Guo F., Zeidel M., Hill W.G. ENaC - Membrane interactions: regulation of channel activity by membrane order. J. Gen. Physiol., 2004, vol. 123, pp. 709-727.
7. Cobos E.J., Entrena J.M., Nieto F.R., Cendán C.M., Del Pozo E. Pharmacology and therapeutic potential of sigma(1) receptor ligands. Curr. Neuropharmacol., 2008, vol. 6, pp. 344-366.
8. Cobos E.J., Del Pozo E., Baeyens J.M. Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells. J. Neurochem., 2007, vol. 102, pp. 812-825.
9. Rousseaux C.G., Greene S.F. Sigma receptors [σRs]: biology in normal and diseased states. J. Recept. Signal. Trans., 2016, vol. 36, pp. 327-388.
10. Hellewell S.B., Bruce A., Feinstein G., Orringer J., Williams W., Bowen W.D. Rat liver and kidney contain high densities of sigma 1 and sigma 2 receptors: characterization by ligand binding and photoaffinity labeling. Eur. J. Pharmacol., 1994, vol. 268, pp. 9-18.
11. Su T.-P., Hayashi T., Maurice T., Buch S., Ruoho A.E. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacol. Sci., 2010, vol. 31, pp. 557-566.
12. Carnally S.M., Johannessen M., Henderson R.M., Jackson M.B., Edwardson J. M. Demonstration of a direct interaction between σ-1 receptors and acid-sensing ion channels. Biophys. J., 2010, vol. 98, pp. 1182-1191.
