Sigma-1 Receptor Ligands Chlorpromazine and Trifluoperazine Attenuate Ca Responses in Rat Peritoneal Macrophages.

Sigma-1 receptors are ubiquitous multifunctional ligand-regulated molecular chaperones in the endoplasmic reticulum membrane with a unique history, structure, and pharmacological profile. Sigma-1 receptors bind ligands of different chemical structure and pharmacological action and modulate a wide range of cellular processes in health and disease, including Ca signaling. To elucidate the involvement of sigma-1 receptors in the processes of Ca signaling in macrophages we studied the effect of sigma-1 receptor ligands, phenothiazine neuroleptics chlorpromazine and trifluoperazine, on Ca responses induced by inhibitors of endoplasmic Ca-ATPases thapsigargin and cyclopiazonic acid, as well as by disulfide-containing immunomodulators Glutoxim and Molixan in rat peritoneal macrophages.

Neuroleptic Chlorpromazine Modulates Ca Responses in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor antagonist neuroleptic chlorpromazine significantly inhibits glutoxim- and molixan-induced Ca responses and Ca responses induced by endoplasmic reticulum Са-ATPase inhibitors thapsigargin and cyclopiazonic acid in rat peritoneal macrophages. The results suggest the involvement of sigma-1 receptors in the signaling cascade induced by glutoxim or molixan and leading to intracellular Ca concentration increase and in the regulation of store-dependent Ca entry in macrophages.

Sigma-1 Receptor Agonist Amitriptyline Inhibits Store-Dependent Ca Entry in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist-tricyclic antidepressant amitriptyline-significantly inhibits store-dependent Ca entry, induced by endoplasmic Ca-ATPase inhibitors thapsigargin and cyclopiazonic acid, in rat peritoneal macrophages. The results suggest a possible involvement of sigma-1 receptors in the regulation of store-dependent Ca entry in macrophages.

Sigma-1 Receptor Antagonists Haloperidol and Chlorpromazine Modulate the Effect of Glutoxim on Na Transport in Frog Skin.

Using voltage-clamp technique, the involvement of sigma-1 receptors in the regulation of Na transport in frog skin by the immunomodulatory drug glutoxim was investigated. We have shown for the first time that preincubation of the frog skin with the sigma-1 receptor antagonists haloperidol and chlorpromazine attenuates the stimulatory effect of glutoxim on the Na transport. The results suggest the possible involvement of the sigma-1 receptors in the regulation of Na transport in frog skin epithelium by glutoxim.

Amitriptyline Attenuates Ca Responses Induced by Glutoxim and Molixan in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist, tricyclic antidepressant amitriptyline, significantly inhibits glutoxim- and molixan-induced Ca-responses in rat peritoneal macrophages. The results suggest possible involvement of sigma-1 receptors in the signaling cascade induced by glutoxim or molixan and leading to intracellular Ca concentration increase in macrophages.