Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Possible role of 18-kDa translocator protein (TSPO) in etifoxine-induced reduction of direct twitch responses in isolated rat nerve-skeletal muscle preparations

Plamen I Zagorchev¹, Vesela Yu Kokova² , Elisaveta G Apostolova², Lyudmil P Peychev²

¹Department of Medical Physics and Biophysics; ²Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4000 Plovdiv, Bulgaria.

For correspondence:- Vesela Kokova Email: vesela_uk@abv.bg Tel:+35932602099

Accepted: 15 June 2018 Published: 28 July 2018

Citation: Zagorchev PI, Kokova VY, Apostolova EG, Peychev LP. Possible role of 18-kDa translocator protein (TSPO) in etifoxine-induced reduction of direct twitch responses in isolated rat nerve-skeletal muscle preparations. Trop J Pharm Res 2018; 17(7):1309-1315 doi: 10.4314/tjpr.v17i7.12

© 2018 The authors.
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Abstract

Purpose: To determine the effects of etifoxine on directly-elicited twitch tension of isolated rat nerve-skeletal muscle preparations and to propose a possible explanation of the mechanism of the observed effect.

Methods: Striated muscles contractile activity was elicited by electrical field stimulation. The effects of etifoxine and nifedipine on direct single twitch response were studied.

Results: The results demonstrate that the effect of etifoxine on skeletal muscle depends on the concentrations: low concentrations (10^-8 i2; and 10^-7 i2;) have little effect on twitch tension, whereas higher concentrations (10^-6 i2; and 10^-5 i2;) induced a significant decrease in the direct single twitch response in comparison to controls. The mean IC₅₀ (reduction of directly-elicited twitch tension) of etifoxine was 0.85 x 10^-6 M. The selective L-type calcium channel blocker nifedipine (10^-5 i2;) induced a greater decrease in the muscle force than 10^-6 i2; etifoxine. The different abilities of etifoxine and nifedipine to reduce direct single twitch response may be related to their distinct mechanisms of action. The observed effect of etifoxine could be more complex. Probably etifoxine acts as a non-selective agent not only on L-type calcium channels Ca_v1.1 localized in sarcolemma but also on 18-kDa translocator protein (TSPO) in skeletal muscle.

Conclusion: Etifoxine-induced reduction of direct twitch responses could be attributed to an effect on TSPO and Ca_v1.1. Knowledge of the effects of TSPO ligands on the contraction of skeletal muscle might explain the role of TSPO in muscle contractility.

Keywords: Etifoxine, TSPO, Calcium channels, Direct single twitch response, Striated muscle