Mechanism underlying histamine-induced intracellular Ca²⁺ movement in PC3 human prostate cancer cells

The effect of histamine on intracellular free Ca²⁺ levels ([Ca²⁺]_i) in PC3 human prostate cancer cells and the underlying mechanism were evaluated using fura-2 as a Ca²⁺ dye. Histamine at concentrations between 0.1 and 50 μM increased [Ca²⁺]_i in a concentration-dependent manner with an EC₅₀ value of 1 μM. The [Ca²⁺]_i response comprised an initial rise and a slow decay, which returned to baseline within 3 min. Extracellular Ca²⁺ removal inhibited 50% of the [Ca²⁺]_i signal. In the absence of extracellular Ca²⁺, after cells were treated with 1 μM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor), 10 μM histamine did not increase [Ca²⁺]_i. After pretreatment with 10 μM histamine in a Ca²⁺-free medium for several minutes, addition of 3 mM Ca²⁺ induced [Ca²⁺]_i increases. Histamine (10 μM)-induced intracellular Ca²⁺ release was abolished by inhibiting phospholipase C with 2 μM 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H- pyrrole-2,5-dione (U73122), and by 10 μM pyrilamine but was not altered by 50 μM cimetidine. Collectively, the present study shows that histamine induced [Ca²⁺]_i transients in PC3 human prostate cancer cells by stimulating H1 histamine receptors leading to Ca²⁺ release from the endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, and by inducing Ca²⁺ entry.