SIGMA-1 RECEPTOR ANTAGONIST, COMPOUND BD-1063, ATTENUATES Ca2+ RESPONSES INDUCED BY MOLIXAN IN MACROPHAGES

Abstract

Sigma-1 receptors are ubiquitous multifunctional ligand-operated molecular chaperones in the endoplasmic reticulum membrane with a unique history, structure, and pharmacological profile. Acting as chaperones, sigma-1 receptors modulate a wide range of cellular processes in health and disease, including Ca2+ signaling processes. The pharmacological analogue of oxidized glutathione, drug molixan®, is used as an immunomodulator and cytoprotector in the complex therapy of bacterial, viral and oncological diseases; effective in the prevention and treatment of coronavirus infection COVID-19. To elucidate the involvement of sigma-1 receptors in the effect of molixan on the intracellular Ca2+ concentration in macrophages and in the regulation of Ca2+ signaling processes in macrophages in general, the effect of the sigma-1 receptor selective antagonist, compound BD-1063, on Ca2+ responses induced by molixan in rat peritoneal macrophages was investigated. Using Fura-2AM microfluorimetry we have shown for the first time that compound BD-1063 significantly suppresses both Ca2+ mobilization from intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry, induced by molixan in peritoneal macrophages. The data obtained indicate the involvement of sigma-1 receptors in the complex signaling cascade triggered by molixan and leading to intracellular Ca2+ concentration increase in macrophages. The results also suggest the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.