Tricyclic Antidepressant Amitriptyline Suppresses Ca2+ Responses in Rat Peritoneal Macrophages

Q4 Biochemistry, Genetics and Molecular Biology

Cell and Tissue Biology Pub Date : 2024-08-06 DOI:10.1134/s1990519x24700378

L. S. Milenina, Z. I. Krutetskaya, V. G. Antonov, N. I. Krutetskaya

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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.

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三环类抗抑郁药阿米替林抑制大鼠腹膜巨噬细胞的 Ca2+ 反应

摘要阿米替林是一种三环类抗抑郁药，临床上广泛用于治疗焦虑、抑郁和慢性疼痛。这类药物对细胞过程有多方面的影响。它们的靶点之一是西格玛-1 受体。Sigma-1 受体是位于内质网膜上的分子伴侣，具有独特的结构和药理特征。Sigma-1 受体调节健康和疾病中的许多细胞过程，包括 Ca2+ 信号转导过程。利用 Fura-2AM 荧光 Ca2+ 探针，我们首次发现西格玛-1 受体激动剂，即抗抑郁药阿米替林、在大鼠腹腔巨噬细胞中，能明显抑制内质 Ca2+ ATP 酶抑制剂thapsigargin 和 cyclopiazonic acid，以及含二硫化物的免疫调节剂 glutoxim 和 molixan 引起的细胞内 Ca2+ 储存的 Ca2+ 迁移，以及随后储存依赖的 Ca2+ 进入细胞。研究结果表明，sigma-1 受体参与了谷草昔或莫立善引起的复杂信号级联，导致巨噬细胞内 Ca2+ 浓度升高。数据还表明，sigma-1 受体参与了巨噬细胞内贮存依赖性 Ca2+ 进入的调节。

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来源期刊

Cell and Tissue Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

0.80

自引率

0.00%

发文量

期刊介绍： The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.