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 muM increased [Ca2+](i) in a concentration-dependent manner with an EC50 value of 1 muM. 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 muM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 10 muM histamine did not increase [Ca2+](i). After pretreatment with 10 muM histamine in a Ca2+-free medium for several minutes, addition of 3 mM Ca2+ induced [Ca2+](i) increases. Histamine (10 muM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 muM 1-(6-((17 beta -3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 10 muM pyrilamine but was not altered by 50 LAM 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. (C) 2001 Academic Press.