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Histamine-Induced Increases in Intracellular Free Ca^(2+) Levels in Hepatoma Cells

並列摘要


The effect of histamine on intracellular free Ca^(2+) levels ([Ca^(2+)]i) in HA22/VGH human hepatoma cells were evaluated using fura-2 as a fluorescent Ca2 dye. Histamine (0.2-5μM) increased [Ca^(2+)]i in a concentration-dependent manner with an EC50 value of about 1μM. The [Ca^(2+)]i, response comprised an initial rise, a slow decay, and a sustained phase. Extracellular Ca^(2+) removal inhibited 50% of the [Ca^(2+)] signal. In Ca^(2+)-free medium, after cells were treated with 1μM thapsigargin (an endoplasmic reticulum Ca^(2+) pump inhibitor), 5μM histamine failed to increase [Ca^(2+)]i. After pretreatment with 5⇑M histamine in Ca^(2+)-free medium for 4min, addition of 3mM Ca^(2+) induced a [Ca^(2+) increase of a magnitude 7-fold greater than control. Histamine (5μM)-induced intracellular Ca^(2+) release was abolished by inhibiting phospholipase C with 2μM 1-(6-((17β-3-methoxyestra-1,3,5(10).trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 5μM pyrilamine but was not altered by 50μM cimetidine. Together, this study shows that histamine induced [Ca^(2+)]i1 increases in human hepatoma cells by stimulating H1, but not H2, histamine receptors. The [Ca^(2+)]i signal was caused by Ca^(2+) release from thapsigargin-sensitive endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, accompanied by Ca^(2+) entry.

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