Saint-Petersburg State Pediatric Medical University
from 01.01.2023 until now
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Store-operated Ca2+ entry (SOCE) is the ubiquitous mechanism of regulated Ca2+-entry in eukaryotic cells, activated upon depletion of intracellular Ca2+-stores; participates in regulation of a wide range of cellular processes (exocytosis, gene expression, etc.). After discovery of the important role of SOCE in the pathogenesis of human diseases, such as severe combined immunodeficiency, nasal polyposis, etc., the researcher’s interest in the development of low molecular weight blockers of SOCE increased. To determine the pharmacological characteristics of SOCE in macrophages, it seemed appropriate to study the effect of the pyrazole derivative compound YM-58483 on SOCE induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid (CPA) in rat peritoneal macrophages. Using Fura-2AM microfluorimetry we found that upon addition of YM-58483 during the developed SOCE induced by thapsigargin or CPA almost complete inhibition of SOCE was observed. This suggests that YM-58483 effectively suppresses already developed SOCE in macrophages. In the second series of experiments, we investigated the effect of YM-58483 after Ca2+ entry mechanisms were activated by store depletion. Macrophages were stimulated by CPA or thapsigargin in Ca2+-free medium. After Ca2+-mobilization from the stores, the cells were incubated for 5 min with YM-58483, then Ca2+ entry into the cell was initiated. It was found that under these conditions, YM-58483 also causes a significant suppression of SOCE. Thus, we showed for the first time on rat peritoneal macrophages, that pyrazole derivative YM-58483 effectively inhibits SOCE and is a useful pharmacological tool for studying SOCE in macrophages, as well as in other cell types.
pyrazole derivative compound YM-58483, store-operated Ca2+ entry, peritoneal macrophages
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