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 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 1 microM. 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 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 10 microM histamine did not increase [Ca2+]i. After pretreatment with 10 microM histamine in a Ca2+-free medium for several minutes, addition of 3 mM Ca2+ induced [Ca2+]i increases. Histamine (10 microM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 microM 1-(6-((17 beta-3- methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 10 microM pyrilamine but was not altered by 50 microM 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.
Lee
K C
KC
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
Chang
H T
HT
Chou
K J
KJ
Tang
K Y
KY
Wang
J L
JL
Lo
Y K
YK
Huang
J K
JK
Chen
W C
WC
Su
W
W
Law
Y P
YP
Jan
C R
CR
D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006632:Histamine / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D017136:Ion Transport; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011471:Prostatic Neoplasms; D011738:Pyrilamine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D004963:Estrenes; D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019284:Thapsigargin; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D011738:Pyrilamine; D002118:Calcium; D016257:Fura-2