TY - JOUR

T1 - Ингибиторы циклооксигеназ подавляют Са2+-ответы, вызываемые хлорпромазином в макрофагах

AU - Миленина, Л.С.

AU - Крутецкая, З.И.

AU - Антонов, В.Г.

AU - Крутецкая, Н.И.

N1 - Conference code: XIV

PY - 2019

Y1 - 2019

N2 - Chlorpromazine belongs to the first antipsychotics generation widely used in treatment of mental diseases. A multifaceted influence of chlorpomazine on intracellular processes has been revealed. Earlier we have shown that chlorpromazine increases intracellular Ca2+ concentration, causing Ca2+ mobilization from intracellular Ca2+-stores and subsequent Ca2+-entry from external medium, in rat peritoneal macrophages. However, the mechanisms by which chlorpomazine causes Ca2+-responses are not fully understood. In activation and functioning of immune cells, including macrophages, the arachidonic acid metabolism cascade plays an important role. In macrophages arachidonic acid is oxidized predominantly by cyclooxygenases and lipoxygenases. Therefore, it was useful to investigate the involvement of cyclooxygenase pathway of arachidonic acid metabolism in the effect of phenothiazine neuroleptic chlorpromazine on intracellular Ca2+-concentration in macrophages. Using Fura-2AM microfluorimetry it was shown for the first time that two structurally distinct cyclooxygenase inhibitors acetylsalicylic acid (aspirin) and indomethacin attenuate Ca2+-responses, induced by chlorpromazine in rat peritoneal macrophages. The data obtained suggest the involvement of cyclooxygenases and (or) cyclooxygenase pathway products in the chlorpromazine effect on intracellular Ca2+-concentration in macrophages. The participation of arachidonic acid cascade enzymes in the influence of chlorpromazine on intracellular Ca2+ concentration can be explained by the model of embedding of amphiphilic antipsychotic agents, including phenothiazine neuroleptics, in the membrane inner monolayer. This can lead to a change in membrane fluidity and functioning of membrane-bound enzymes, such as phospholipase A2, which triggers arachidonic acid cascade. In turn, the enzymes and/or products of arachidonic acid metabolism are involved in the formation of chlorpromazine-induced Ca2+ responses.

AB - Chlorpromazine belongs to the first antipsychotics generation widely used in treatment of mental diseases. A multifaceted influence of chlorpomazine on intracellular processes has been revealed. Earlier we have shown that chlorpromazine increases intracellular Ca2+ concentration, causing Ca2+ mobilization from intracellular Ca2+-stores and subsequent Ca2+-entry from external medium, in rat peritoneal macrophages. However, the mechanisms by which chlorpomazine causes Ca2+-responses are not fully understood. In activation and functioning of immune cells, including macrophages, the arachidonic acid metabolism cascade plays an important role. In macrophages arachidonic acid is oxidized predominantly by cyclooxygenases and lipoxygenases. Therefore, it was useful to investigate the involvement of cyclooxygenase pathway of arachidonic acid metabolism in the effect of phenothiazine neuroleptic chlorpromazine on intracellular Ca2+-concentration in macrophages. Using Fura-2AM microfluorimetry it was shown for the first time that two structurally distinct cyclooxygenase inhibitors acetylsalicylic acid (aspirin) and indomethacin attenuate Ca2+-responses, induced by chlorpromazine in rat peritoneal macrophages. The data obtained suggest the involvement of cyclooxygenases and (or) cyclooxygenase pathway products in the chlorpromazine effect on intracellular Ca2+-concentration in macrophages. The participation of arachidonic acid cascade enzymes in the influence of chlorpromazine on intracellular Ca2+ concentration can be explained by the model of embedding of amphiphilic antipsychotic agents, including phenothiazine neuroleptics, in the membrane inner monolayer. This can lead to a change in membrane fluidity and functioning of membrane-bound enzymes, such as phospholipase A2, which triggers arachidonic acid cascade. In turn, the enzymes and/or products of arachidonic acid metabolism are involved in the formation of chlorpromazine-induced Ca2+ responses.

KW - хлорпромазин

KW - циклооксигеназы

KW - внутриклеточная концентрация Са2+

KW - перитонеальные макрофаги

KW - chlorpromazine

KW - intracellular Ca2+-concentration

KW - cyclooxygenases

KW - peritoneal macrophages

M3 - статья

VL - 4

SP - 73

EP - 76

JO - АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ

JF - АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ

SN - 2499-9962

IS - 1

T2 - XIV Международная научная конференция "Актуальные вопросы биологической физики и химии, посвященная 60-летию кафедры биофизики физического факультета МГУ. БФФХ-2019"

Y2 - 21 November 2019 through 24 November 2019

ER -