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Regulation of nuclear calcium uptake by inositol phosphates and external calcium
1Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Abstract:
Factors affecting Ins(1,3,4,5)P4-mediated nuclear Ca2+ uptake are investigated, which include Ins(1,3,4,5)P4 receptor ligand specificity and free external Ca2+ concentrations. Among various inositol phosphates examined, Ins(1,3,4,5)P4, Ins(3,4,5,6)P4, and Ins(1,3,4,5,6)P5 can also stimulate 45Ca2+ influx into isolated rat liver nuclei by activating the Ins(1,3,4,5)P4 receptor-mediated Ca2+ uptake into the nucleus. The EC50 values of these polyphosphates range between 200 and 300 nM, which are 3-4 folds higher than that of Ins(1,3,4,5)P4. It is plausible that these polyphosphates in conjunction with Ins(1,3,4,5)P4 take part in the regulation of nuclear Ca2+ uptake in view of their intracellular levels during cell activation. Moreover, the inositol phosphate-induced Ca2+ uptake is facilitated by increasing Ca2+ levels in the uptake milieu, suggesting a possible link between cytosolic and nuclear Ca2+ signals through the Ins(1,3,4,5)P4 receptor.
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