Haloperidol, a sigma-1 receptor antagonist, inhibits Ca²⁺ responses in rat peritoneal macrophages

Abstract

Sigma-1 receptors are ubiquitous multifunctional ligand-operated molecular chaperones in the endoplasmic reticulum membrane and have a unique history, structure, and pharmacological profile. Sigma-1 receptors modulate a wide range of cellular processes in health and disease and Ca2+ signaling processes. Using the Ca2+ sensitive fluorescent ratiometric dye Fura-2AM, it has been shown that neuroleptic (haloperidol, an antagonist of sigma-1 receptors) significantly suppresses Ca2+ mobilization from intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry, induced by thapsigargin and cyclopiazonic acid, as inhibitors of endoplasmic reticulum Ca2+-ATPases, and also by glutoxim and molixan, disulfide-containing immunomodulatory drugs, in rat peritoneal macrophages. Findings of the study revealed that sigma-1 receptors are involved in the complex signaling cascade triggered by glutoxim or molixan that leads to the increase in the intracellular Ca2+ concentration in macrophages and participate in regulation of store-dependent Ca2+ entry in macrophages.