Publication Date:
1988-11-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, T D -- Dean, N M -- Boynton, A L -- CA 39745/CA/NCI NIH HHS/ -- CA 42942/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1988 Nov 25;242(4882):1176-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2847317" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/*metabolism
;
*Calcium Channels
;
Calcium-Transporting ATPases/metabolism
;
Cell Membrane Permeability
;
Epithelium/metabolism
;
Inositol 1,4,5-Trisphosphate
;
Inositol 1,4,5-Trisphosphate Receptors
;
Inositol Phosphates/metabolism/*pharmacology
;
Liver/drug effects/*metabolism
;
Liver Neoplasms, Experimental/metabolism
;
Rats
;
Receptors, Cell Surface/metabolism
;
*Receptors, Cytoplasmic and Nuclear
;
Sugar Phosphates/*pharmacology
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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