The skin of amphibians is a classic model object for the study of transepithelial ion transport mechanisms. Previously, we found that Na+ transport in frog skin epithelial cells is modulated by oxidizing and reducing agents. For the first time we showed that oxidized glutathione (GSSG) and drug glutoxim® (disodium salt of GSSG with a nano additive of a d-metal, PHARMA-VAM, Saint-Petersburg), mimic insulin effect and stimulate transepithelial Na+ transport when applied to the frog skin basolateral surface. Sigma-1 receptors are unique ligand-regulated molecular chaperones widely expressed in central nervous system and in peripheral tissues, including kidney and liver cells. Sigma-1 receptors interact with target proteins, including ion channels and receptors, and modulate many cellular processes. We have previously shown that sigma-1 receptor ligand neuroleptic trifluoperazine (TFP) inhibits Na+ transport in frog skin. It is known that some of the clinical cases require concomitant use of immunomodulators and neuroleptics. Thus, it was appropriate to study the involvement of sigma-1 receptors in glutoxim effect on Na+ transport in frog skin. Phenothiazine derivative neuroleptic TFP, the ligand of sigma-1 receptor, was used in our experiments. Using voltage-clamp technique, we have shown for the first time that frog skin preincubation with 20 mg/ml TFP attenuates the stimulatory effect of 100 mg/ml glutoxim on Na+ transport. The results indicate the involvement of sigma-1 receptors in signaling cascades triggered by glutoxim in frog skin epithelium and leading to Na+ transport stimulation and also suggest that a combined use of drug glutoxim and phenothiazine derivatives in clinical practice is undesirable.
frog skin, transepithelial Na+ transport, glutoxim, sigma-1 receptors, trifluoperazine
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