TY - JOUR

T1 - Sigma-1 receptor ligands chlorpromazine and trifluoperazine attenuate Ca2+ responses in rat peritoneal macrophages

AU - Milenina, L. S.

AU - Krutetskaya, Z. I.

AU - Antonov, V. G.

AU - Krutetskaya, N. I.

N1 - L. S. Milenina, Z. I. Krutetskaya, V. G. Antonov, N. I. Krutetskaya. Sigma-1 receptor ligands chlorpromazine and trifluoperazine attenuate Ca2+ responses in rat peritoneal macrophages. Cell and Tissue Biology. V. 16. N. 3. 2022. P. 233-244.

PY - 2022

Y1 - 2022

N2 - 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 Ca2+ signaling. To elucidate the involvement of sigma1 receptors in the processes of Ca2+ signaling in macrophages we studied the effect of sigma-1 receptor ligands, phenothiazine neuroleptics chlorpromazine and trifluoperazine, on Ca2+ responses induced by inhibitors of endoplasmic Ca2+–ATPases thapsigargin and cyclopiazonic acid, as well as by disulfide-containing immunomodulators Glutoxim and Molixan in rat peritoneal macrophages. Using Fura-2AM microfluorimetry we showed for the first time that chlorpromazine and trifluoperazine inhibit both phases of Ca2+ responses induced by Glutoxim, Molixan, thapsigargin, and cyclopiazonic acid in rat peritoneal macrophages. The data obtained indicate the participation of sigma-1 receptors in a complex signaling cascade caused by Glutoxim or Molixan and leading to an increase in intracellular Ca2+ concentration in macrophages. The results also indicate the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+entry in macrophages.

AB - 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 Ca2+ signaling. To elucidate the involvement of sigma1 receptors in the processes of Ca2+ signaling in macrophages we studied the effect of sigma-1 receptor ligands, phenothiazine neuroleptics chlorpromazine and trifluoperazine, on Ca2+ responses induced by inhibitors of endoplasmic Ca2+–ATPases thapsigargin and cyclopiazonic acid, as well as by disulfide-containing immunomodulators Glutoxim and Molixan in rat peritoneal macrophages. Using Fura-2AM microfluorimetry we showed for the first time that chlorpromazine and trifluoperazine inhibit both phases of Ca2+ responses induced by Glutoxim, Molixan, thapsigargin, and cyclopiazonic acid in rat peritoneal macrophages. The data obtained indicate the participation of sigma-1 receptors in a complex signaling cascade caused by Glutoxim or Molixan and leading to an increase in intracellular Ca2+ concentration in macrophages. The results also indicate the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+entry in macrophages.

KW - trifluoperazine

KW - chlorpromazine

KW - sigma-1 receptors

KW - peritoneal macrophages

KW - intracellular Ca2+ concentration

M3 - Article

VL - 16

SP - 233

EP - 244

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 3

ER -