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. 2025 Jun;83(2):2453-2459.
doi: 10.1007/s12013-024-01654-6. Epub 2024 Dec 28.

Interaction Between Allopregnanolone and Amiloride Binding Sites on the GABAA Receptor

Julia V Bukanova  1 , Rodion V Kondratenko  1 , Elena I Solntseva  2
Affiliations

Interaction Between Allopregnanolone and Amiloride Binding Sites on the GABAA Receptor

Julia V Bukanova et al. Cell Biochem Biophys. 2025 Jun.

Abstract

Allopregnanolone (Allo) is a positive allosteric modulator of the GABAA receptor, and amiloride (Ami) is a competitive antagonist of the GABAA receptor. The purpose of this work was to study the combined effect of Allo and Ami on functional activity of GABAA receptor. The GABA-induced chloride current (IGABA) was measured in isolated Purkinje cells of rat cerebellum using the patch-clamp technique and a system of fast application. Our results indicate that Allo suppresses the inhibitory effect of Ami on IGABA, the IC50 value of Ami concentration-response curve was increased from 164 to 547 µM (P < 0.001) in the presence of Allo. Next, GABA concentration-response curves (EC50 = 5.8 µM) were constructed in the presence of Allo (EC50 = 1.2 µM), Ami (EC50 = 25.5 µM), and the combination of Allo+Ami (EC50 = 3.2 µM). Changes in EC50 values as a percentage relative to the control were calculated. The blocking effect of Ami is reduced in the presence of Allo (340% vs 150%, P < 0.01) and the potentiating effect of Allo does not change in the presence of Ami (78% vs 87%, P > 0.05). The results suggest that there is an allosteric relationship between the Allo and Ami binding sites on GABAA receptor that operates in one direction, from Allo sites to Ami site, but not vice versa.

Keywords: Allopregnanolone; Amiloride; GABAA-receptor; Patch-clamp; Purkinje cells.

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Conflict of interest statement

Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests.

References

    1. Sigel, E., & Steinmann, M. E. (2012). Structure, function, and modulation of GABA(A) receptors. Journal of Biological Chemistry, 287, 40224–40231. https://doi.org/10.1074/jbc.R112.386664 . - DOI - PubMed - PMC
    1. Olsen, R. W. (2018). GABAA receptor: Positive and negative allosteric modulators. Neuropharmacology, 136, 10–22. https://doi.org/10.1016/j.neuropharm.2018.01.036 . - DOI - PubMed - PMC
    1. Bukanova, J. V., Kondratenko, R. V., & Solntseva, E. I. (2022). Positive allosteric modulators of GABAA receptor restore chloride current from blockade by competitive antagonists in a ligand-dependent manner. The Journal of Steroid Biochemistry and Molecular Biology, 224, 106158. https://doi.org/10.1016/j.jsbmb.2022.106158 . - DOI - PubMed
    1. Bukanova, J. V., Solntseva, E. I., & Skrebitsky, V. G. (2024). Factors promoting the release of picrotoxin from the trap in the GABA(A) receptor pore. Neurochemistry International, 175, 105703. https://doi.org/10.1016/j.neuint.2024.105703 . - DOI - PubMed
    1. Vale, C., Pomés, A., Rodríguez-Farré, E., & Suñol, C. (1997). Allosteric interactions between gamma-aminobutyric acid, benzodiazepine and picrotoxinin binding sites in primary cultures of cerebellar granule cells. Differential effects induced by gamma- and delta-hexachlorocyclohexane. European Journal of Pharmacology, 319, 343–353. https://doi.org/10.1016/s0014-2999(96)00866-7 . - DOI - PubMed

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