Cell and Tissue BiologyCell and Tissue BiologyЦитология0041-37713034-6061The Russian Academy of Sciences66961410.31857/S0041377124020069RJYORGArticlesСтатьиResearch ArticleTricyclic antidepressant amitriptyline attenuates Ca2+ responses in rat peritoneal macrophagesТрициклический антидепрессант амитриптилин подавляет Са2+-ответы в перитонеальных макрофагах крысыMileninaL. S.МиленинаЛ. С.
Russian Federation

Chair of Biophysics

Кафедра биофизики

l.milenina@spbu.ruKrutetskayaZ. I.КрутецкаяЗ. И.
Russian Federation

Chair of Biophysics

Кафедра биофизики

z.krutetskaya@spbu.ruAntonovV. G.АнтоновВ. Г.
Russian Federation

Chair of Biochemistry

Кафедра биохимии

l.milenina@spbu.ruKrutetskayaN. I.КрутецкаяН. И.
Russian Federation

Chair of Biophysics

Кафедра биофизики

l.milenina@spbu.ruSt. Petersburg State UniversityСанкт-Петербургский государственный университетSt. Petersburg State Pediatric Medical UniversityСанкт-Петербургский государственный педиатрический медицинский университет1503202466216117227022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0041-3771/article/view/669614

Amitriptyline is a tricyclic antidepressant widely used in clinical practice for the treatment of anxiety, 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 endoplasmic reticulum membrane; they are characterized by a unique structure and pharmacological profile. Sigma-1 receptors regulate many cellular processes in health and disease, including Ca2+ signaling. Using Fura-2AM microfluorimetry, it was shown for the first time that sigma-1 receptor agonist, antidepressant amitriptyline, significantly suppresses both Ca2+ mobilization from intracellular Ca2+-stores and subsequent store-dependent Ca2+ entry into cells, induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid, as well as disulfide-containing immunomodulators glutoxim and molixan, in rat peritoneal macrophages. The results suggest the involvement of sigma-1 receptors in a complex signaling cascade induced by glutoxim or molixan, leading to an increase of intracellular Ca2+ concentration in macrophages. The results also indicate the participation of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.

Амитриптилин относится к трициклическим антидепрессантам, широко используемым в клинической практике для терапии тревожно-депрессивных состояний и хронической боли. Эти препараты оказывают многогранное влияние на клеточные процессы. Одной из их мишеней служат рецепторы сигма-1 – молекулярные шапероны, расположенные в мембране эндоплазматического ретикулума. Им свойственны уникальная структура и фармакологический профиль. Рецепторы сигма-1 регулируют многие клеточные процессы в норме и патологии, в том числе процессы Ca2+-сигнализации. С использованием флуоресцентного Са2+-зонда Fura-2AM впервые показано, что агонист рецепторов сигма-1 антидепрессант амитриптилин существенно подавляет как мобилизацию Са2+ из внутриклеточных Са2+-депо, так и последующий депозависимый вход Са2+ в клетки, вызываемые ингибиторами эндоплазматических Са2+-АТФаз тапсигаргином и циклопьязониковой кислотой, а также дисульфидсодержащими иммуномодуляторами глутоксимом и моликсаном, в перитонеальных макрофагах крысы. Результаты указывают на участие рецепторов сигма-1 в вызываемом глутоксимом или моликсаном комплексном сигнальном каскаде, приводящем к увеличению внутриклеточной концентрации Са2+ в макрофагах. Данные свидетельствуют также об участии рецепторов сигма-1 в регуляции депозависимого входа Са2+ в макрофагах.

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