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Fig. 1. Endocannabinoids trigger Ca2+ signaling and ER depletion in human endothelial cells. (A) Comparison of the effects of 100 µM histamine (n=18) and 10 µM anandamide (n=31) on cytosolic free-Ca2+ concentration in the presence of 2 mM extracellular Ca2+. (B) Cytoplasmic free-Ca2+ concentration upon stimulation with 100 µM histamine (n=19) and 10 µM anandamide (n=21) in the absence of extracellular Ca2+, followed by re-addition of 2 mM extracellular Ca2+ to reveal store-operated Ca2+ entry due to previous ER depletion. (C) Comparison of the effects of 100 µM histamine (n=4) and 10 µM anandamide (n=3) on free ER Ca2+ concentration in the absence of extracellular Ca2+, followed by re-addition of 2 mM extracellular Ca2+ to visualize ER Ca2+ refilling efficiency. (D) Concentration-response curves for anandamide (n=10) and metanandamide (n=10) on peak responses of cytosolic Ca2+ elevation in the nominal absence of extracellular Ca2+. Cytosolic (A,B,D) and ER (C) Ca2+ concentrations were recorded using fura-2 and YC4er, respectively. *P<0.01 versus histamine.