Abstract
The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in Chang liver cells were investigated by using fura-2 as a Ca2+ dye. Histamine (0.2–50 μM) increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 0.8 μM. The [Ca2+]i response comprised an initial rise, a slow decay, and a sustained phase. Extracellular Ca2+ removal inhibited 50% of the maximum [Ca2+]i signal and abolished the sustained phase. After pretreatment with 5 μM histamine in Ca2+-free medium for 4 min, addition of 3 mM Ca2+ induced a [Ca2+]i increase with a magnitude 7-fold greater than control. In Ca2+-free medium, after treatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 5 μM histamine failed to increase [Ca2+]i. Histamine (5 μM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 μM 1-(6-((17b-3-methoxyestra-1,3,5Citation-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; U73122), and by 5 μM pyrilamine but was unaltered by 50 μM cimetidine. Collectively, the present study shows that histamine caused significant [Ca2+]i increases in Chang liver cells by stimulating H1 histamine receptors. The [Ca2+]i increase was triggered by Ca2+ release from thapsigargin-sensitive endoplasmic reticulum stores in an inositol 1,4,5-trisphosphate-sensitive fashion, and was accompanied by Ca2+ entry from extracellular space.