Citrus bergamia Risso elevates intracellular Ca²⁺ in human vascular endothelial cells due to release of Ca²⁺ from primary intracellular stores

The purpose of the present study is to examine the effects of essential oil of Citrus bergamia Risso (bergamot, BEO) on intracellular Ca²⁺ in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca²⁺ concentration [ Ca 2 + ] i. In the presence of extracellular Ca²⁺, BEO increased [ Ca 2 + ] i, which was partially inhibited by a nonselective Ca²⁺ channel blocker La ³⁺. In Ca²⁺-free extracellular solutions, BEO increased [ Ca 2 + ] i in a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca²⁺. BEO-induced [ Ca 2 + ] i increase was partially inhibited by a Ca²⁺-induced Ca²⁺ release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP₃)-gated Ca²⁺ channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased [ Ca 2 + ] i in the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca²⁺ uptake. In addition, store-operated Ca ²⁺ entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca²⁺ from primary intracellular stores via Ca ²⁺-induced and IP3-mediated Ca²⁺ release and affect promotion of Ca²⁺ influx, likely via an SOC mechanism.