Release of intracellular calcium and stimulation of cell growth by ATP and histamine in human ovarian cancer cells (SKOV-3).
The effects of ATP and histamine on cell proliferation and intracellular calcium concentrations ([Ca2+]i) were examined in the human ovarian cancer cell line SKOV-3. Micromolar concentrations of ATP induced a biphasic increase in [Ca2+]i representing a rapid rise to a peak level followed by a smaller but more sustained phase. When influx of extracellular calcium was blocked by calcium chelation to EGTA, the ATP-stimulated rise in [Ca2+]i was rapid and only monophasic. Histamine, in contrast to ATP, caused only a monophasic rise in [Ca2+]i both in the presence and absence of external calcium. The histaminergic H1 receptor antagonist pyrilamine, but not the H2 receptor antagonist cimetidine, totally blocked rises in [Ca2+]i caused by histamine. Fetal calf serum (FCS) induced a slow and monophasic increase in [Ca2+]i in these cells, distinctly different from rises in [Ca2+]i caused by ATP and histamine. Inclusion of low micromolar concentrations of ATP in the growth medium stimulated proliferation of these cells, while higher concentrations (100 microM-1 mM) significantly decreased cellular proliferation. Histamine, in micromolar concentrations, also stimulated cell proliferation. From these results it was concluded that the release of intracellularly bound Ca2+ following receptor stimulation is sufficient to induce cellular proliferation in SKOV-3 cells.
Batra
S
S
Department of Pharmacology, University of Lund, Sweden.
Fadeel
I
I
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D006632:Histamine; D000255:Adenosine Triphosphate; D002118:Calcium