Tricyclic Antidepressant Amitriptyline Suppresses Ca2+ Responses in Rat Peritoneal Macrophages

• Published in: Cell and tissue biology Vol. 18; no. 4; pp. 439 - 450
• Main Authors: Milenina, L. S., Krutetskaya, Z. I., Antonov, V. G., Krutetskaya, N. I.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2024; Springer Nature B.V
• Subjects: Amitriptyline; Biomedical and Life Sciences; Calcium (intracellular); Calcium influx; Calcium signalling; Cell Biology; Chronic pain; Cyclopiazonic acid; Endoplasmic reticulum; Immunomodulation; Intracellular; Intracellular signalling; Life Sciences; Macrophages; Peritoneum; Thapsigargin; sigma-1 receptors; amitriptyline; concentration; peritoneal macrophages; intracellular Ca
• ISSN: 1990-519X; 1990-5203
• DOI: 10.1134/S1990519X24700378

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 Ca
2+
signaling. Using Fura-2AM fluorescent Ca
2+
probe, we showed for the first time that sigma-1 receptor agonist, the antidepressant amitriptyline, significantly suppresses Ca
2+
mobilization from the intracellular Ca
2+
stores and subsequent store-dependent Ca
2+
entry into cells caused by inhibitors of endoplasmic Ca
2+
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 Ca
2+
concentration in macrophages. Data also indicate that sigma-1 receptors participate in the regulation of store-dependent Ca
2+
entry in macrophages.