TY - JOUR

T1 - Tricyclic Antidepressant Amitriptyline Suppresses Ca2+ Responses in Rat Peritoneal Macrophages

AU - Миленина, Лидия Сергеевна

AU - Крутецкая, Зоя Иринарховна

AU - Антонов, Виктор Георгиевич

AU - Крутецкая, Нина Иринарховна

N1 - L.S. Milenina, Z.I. Krutetskaya, V.G. Antonov, N.I. Krutetskaya. Tricyclic Antidepressant Amitriptyline Suppresses Ca2+ Responses in Rat Peritoneal Macrophages. Cell and Tissue Biology. 2024. Vol. 18. No. 4. p. 439–450.

PY - 2024/8/1

Y1 - 2024/8/1

N2 - Abstract: Amitriptyline is a tricyclic antidepressant widely used in clinical practice for the treatment of an-xiety and depression and chronic pain. These drugs have a multifaceted effect on cellular processes. One of their targets is sigma-1 receptors. Sigma-1 receptors are molecular chaperones located in the membrane of the endoplasmic reticulum; they are characterized by a unique structure and pharmacological profile. Sigma-1 receptors regulate many cellular processes in health and disease, including processes of Ca2+ signaling. Using Fura-2AM fluorescent Ca2+ probe, we showed for the first time that sigma-1 receptor agonist, the antidepressant amitriptyline, significantly suppresses Ca2+ mobilization from the intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry into cells caused by inhibitors of endoplasmic Ca2+ ATPases thapsigargin and cyclopiazonic acid, as well as the disulfide-containing immunomodulators glutoxim and molixan, in rat peritoneal macrophages. The results indicate the participation of sigma-1 receptors in the complex signaling cascade caused by glutoxim or molixan, leading to an increase in intracellular Ca2+ concentration in macrophages. Data also indicate that sigma-1 receptors participate in the regulation of store-dependent Ca2+ entry in macrophages.

AB - Abstract: Amitriptyline is a tricyclic antidepressant widely used in clinical practice for the treatment of an-xiety and depression and chronic pain. These drugs have a multifaceted effect on cellular processes. One of their targets is sigma-1 receptors. Sigma-1 receptors are molecular chaperones located in the membrane of the endoplasmic reticulum; they are characterized by a unique structure and pharmacological profile. Sigma-1 receptors regulate many cellular processes in health and disease, including processes of Ca2+ signaling. Using Fura-2AM fluorescent Ca2+ probe, we showed for the first time that sigma-1 receptor agonist, the antidepressant amitriptyline, significantly suppresses Ca2+ mobilization from the intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry into cells caused by inhibitors of endoplasmic Ca2+ ATPases thapsigargin and cyclopiazonic acid, as well as the disulfide-containing immunomodulators glutoxim and molixan, in rat peritoneal macrophages. The results indicate the participation of sigma-1 receptors in the complex signaling cascade caused by glutoxim or molixan, leading to an increase in intracellular Ca2+ concentration in macrophages. Data also indicate that sigma-1 receptors participate in the regulation of store-dependent Ca2+ entry in macrophages.

KW - amitriptyline

KW - intracellular Ca2+ concentration

KW - peritoneal macrophages

KW - sigma-1 receptors

UR - https://www.mendeley.com/catalogue/cf559335-459d-3c2c-b639-b06de6fc0416/

U2 - 10.1134/s1990519x24700378

DO - 10.1134/s1990519x24700378

M3 - Article

VL - 18

SP - 439

EP - 450

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 4

ER -