Histamine-Induced increases in intracellular free Ca2+ levels in hepatoma cells.
The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in HA22/VGH human hepatoma cells were evaluated using fura-2 as a fluorescent Ca2+ dye. Histamine (0.2-5 microM) increased [Ca2+]i in a concentration-dependent manner with an EC50 value of about 1 microM. The [Ca2+]i response comprised an initial rise, a slow decay, and a sustained phase. Extracellular Ca2+ removal inhibited 50% of the [Ca2+]i signal. In Ca2+-free medium, after cells were treated with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 5 microM histamine failed to increase [Ca2+]i. After pretreatment with 5 microM histamine in Ca2+-free medium for 4 min, addition of 3 mM Ca2+ induced a [Ca2+]i increase of a magnitude 7-fold greater than control. Histamine (5 microM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 5 microM pyrilamine but was not altered by 50 microM cimetidine. Together, this study shows that histamine induced [Ca2+]i increases in human hepatoma cells by stimulating H1, but not H2, histamine receptors. The [Ca2+]i signal was caused by Ca2+ release from thapsigargin-sensitive endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, accompanied by Ca2+ entry.
Cheng
J S
JS
Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan, ROC.
Lee
K C
KC
Wang
J L
JL
Tseng
L L
LL
Chou
K J
KJ
Tang
K Y
KY
Jan
C R
CR
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D002927:Cimetidine / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008113:Liver Neoplasms; D011738:Pyrilamine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D011738:Pyrilamine; D002118:Calcium; D016257:Fura-2