Нейролептики подавляют Са2+-ответы, вызываемые глутоксимом и моликсаном в макрофагах

Abstract

Haloperidol (butyrophenone derivative) and phenothiazine derivatives chlorpromazine and trifluoperazine belong to the typical first-generation neuroleptics and are widely used in clinical practice for treatment of schizophrenia and other mental diseases. Their multifaceted effect on cellular processes is well known. Thus, a high affinity of typical neuroleptics for sigma-1 receptors was revealed. 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. To elucidate the involvement of sigma-1 receptors in Ca2+ signaling processes in macrophages, the effect of sigma-1 receptor ligands on Ca2+ responses induced by disulfide-containing immunomodulators glutoxim and molixan in rat peritoneal macrophages was investigated. Using Fura-2AM microfluorimetry we have shown that haloperidol, chlorpromazine and trifluoperazine significantly suppress both Ca2+ mobilization from intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry, induced by glutoxim or molixan in peritoneal macrophages. The data obtained indicate the possible involvement of sigma-1 receptors in the complex signaling cascade triggered by glutoxim or 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.