Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells.

has been widely used as an anti-inflammatory and anti-lipogenic agent in traditional medicine. Recently, was reported to prevent hypertension by improving vascular function. This study evaluated the effects of and its major component lancemaside A on cytosolic calcium concentration in vascular endothelial cells and vascular smooth muscle cells. Cytosolic calcium concentration was measured using fura-2 AM fluorescence. or lancemaside A increased the cytosolic calcium concentration by releasing Ca from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca entry into endothelial cells and vascular smooth muscle cells from extracellular sources. The - and lancemaside A-induced cytosolic calcium concentration increases were significantly inhibited by lanthanum, an inhibitor of non-selective cation channels, in both endothelial cells and vascular smooth muscle cells. Moreover, and lancemaside A significantly inhibited store-operated Ca entry under pathological extracellular Ca levels. In Ca-free extracellular fluid, increases in the cytosolic calcium concentration induced by or lancemaside A were significantly inhibited by U73122, an inhibitor of phospholipase C, and 2-APB, an inositol 1,4,5-trisphosphate receptor antagonist. In addition, dantrolene treatment, which inhibits Ca release through ryanodine receptor channels, also inhibited - or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway. These results suggest that and lancemaside A increase the cytosolic calcium concentration through the non-selective cation channels and phospholipase C/inositol 1,4,5-trisphosphate pathways under physiological conditions and inhibit store-operated Ca entry under pathological conditions in endothelial cells and vascular smooth muscle cells. or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.