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

• Published in: Biophysics (Oxford) 2023, Vol.68 (4), p.552-560
• Main Authors: Milenina, L. S., Krutetskaya, Z. I., Antonov, V. G., Krutetskaya, N. I.
• Format: Article
• Language: English
• Subjects: Biological and Medical Physics; Biophysics; Ca2+-transporting ATPase; Calcium (intracellular); Calcium antagonists; Calcium influx; Calcium signalling; Cell Biophysics; Cyclopiazonic acid; Endoplasmic reticulum; Haloperidol; Immunomodulation; Intracellular; Macrophages; Peritoneum; Physics; Physics and Astronomy; Thapsigargin
• ISSN: 0006-3509; 1555-6654
• DOI: 10.1134/S0006350923040140

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 Ca 2+ signaling processes. Using the Fura-2AM fluorescent Ca 2+ probe, we have shown that sigma-1 receptor antagonist neuroleptic haloperidol significantly suppressed the mobilization of Ca 2+ from intracellular Ca 2+ stores and the subsequent store-dependent Ca 2+ entry into cells caused by endoplasmic Ca 2+ -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 Ca 2+ concentration in macrophages, as well as the involvement of sigma-1 receptors in the regulation of store-dependent Ca 2+ entry in macrophages.