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Haloperidol, a Sigma-1 Receptor Antagonist, Inhibits Ca2+ Responses in Rat Peritoneal Macrophages

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Abstract

Sigma-1 receptors are ubiquitous multifunctional ligand-regulated molecular chaperons in the membrane of the endoplasmic reticulum, having a unique history, structure and pharmacological profile. Sigma-1 receptors modulate a wide range of cellular processes in normal and pathological conditions, inclu-ding Ca2+ signaling processes. Using the Fura-2AM fluorescent Ca2+ probe, we have shown that sigma-1 receptor antagonist neuroleptic haloperidol significantly suppressed the mobilization of Ca2+ from intracellular Ca2+ stores and the subsequent store-dependent Ca2+ entry into cells caused by endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid, as well as immunomodulators glutoxim and molixan in rat peritoneal macrophages. The results indicated the participation of sigma-1 receptors in the complex signaling cascade caused by glutoxim or molixan and leading to an increase in intracellular Ca2+ concentration in macrophages, as well as the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.

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Funding

The work was carried out within the framework of the contracts of St. Petersburg State University for the performance of research works, projects no. 01/18-R&D dated 05.03.2018 and no. 05/03-20 dated March 12, 2020.

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Correspondence to L. S. Milenina.

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CONFLICT OF INTEREST

The authors of this article declare that there is no conflict of interest.

COMPLIANCE WITH ETHICAL STANDARDS

The animals were kept and all manipulations with them were carried out in accordance with regulatory documents and the requirements of the Order of the Ministry of Health of the Russian Federation No. 267 dated 06/19/03 “On approval of the rules of laboratory practice in the Russian Federation.”

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Translated by E. Puchkov

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Abbreviations: CPA, cyclopiazonic acid; [Ca2+]i, intracellular concentration of Ca2+.

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Milenina, L.S., Krutetskaya, Z.I., Antonov, V.G. et al. Haloperidol, a Sigma-1 Receptor Antagonist, Inhibits Ca2+ Responses in Rat Peritoneal Macrophages. BIOPHYSICS 68, 552–560 (2023). https://doi.org/10.1134/S0006350923040140

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