Inositol 1,3,4,5-tetrakisphosphate induces Ca2+ sequestration in rat liver cells.
Inositol 1,4,5-trisphosphate [I(1,4,5)P3] is a second messenger generated along with diacylglycerol upon the binding of various physiological agents with their cell surface receptors. I(1,4,5)P3 mobilizes Ca2+ from intracellular storage sites through a receptor-coupled mechanism, and the subsequent increased intracellular free calcium ion concentration [( Ca2+]i) activates a multitude of cellular responses. Electropermeabilized neoplastic rat liver epithelial (261B) cells were used to study Ca2+ sequestration, a process that reverses the elevated [Ca2+]i to resting levels and replenishes intracellular Ca2+ pools. Although I (1,4,5)P3-mobilized Ca2+ is readily sequestered into storage pools by the action of Ca2+-adenosine triphosphatases, Ca2+ mobilized by addition of the nonmetabolized inositol trisphosphate isomer I(2,4,5)P3 is not sequestered, suggesting that metabolism is necessary to eliminate the stimulus for Ca2+ release. Several inositol phosphate compounds were examined for their ability to lower the buffer [Ca2+] to determine if a specific I(1,4,5)P3 metabolite might be involved in stimulating Ca2+ sequestration; of these, I(1,3,4,5)P4 alone was found to induce Ca2+ sequestration, demonstrating a physiological role for this inositol trisphosphate metabolite.
Hill
T D
TD
Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
Dean
N M
NM
Boynton
A L
AL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002463:Cell Membrane Permeability; D004848:Epithelium / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium