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• W2016387671 abstract "Most animal cells express mixtures of the three subtypes of inositol 1,4,5-trisphosphate receptor (IP(3)R) encoded by vertebrate genomes. Activation of each subtype by different agonists has not hitherto been examined in cells expressing defined homogenous populations of IP(3)R. Here we measure Ca(2+) release evoked by synthetic analogues of IP(3) using a Ca(2+) indicator within the lumen of the endoplasmic reticulum of permeabilized DT40 cells stably expressing single subtypes of mammalian IP(3)R. Phosphorylation of (1,4,5)IP(3) to (1,3,4,5)IP(4) reduced potency by ~100-fold. Relative to (1,4,5)IP(3), the potencies of IP(3) analogues modified at the 1-position (malachite green (1,4,5)IP(3)), 2-position (2-deoxy(1,4,5)IP(3)) or 3-position (3-deoxy(1,4,5)IP(3), (1,3,4,5)IP(4)) were similar for each IP(3)R subtype. The potency of an analogue, (1,4,6)IP(3), in which the orientations of the 2- and 3-hydroxyl groups were inverted, was also reduced similarly for all three IP(3)R subtypes. Most analogues of IP(3) interact similarly with the three IP(3)R subtypes, but the decrease in potency accompanying removal of the 1-phosphate from (1,4,5)IP(3) was least for IP(3)R3. Addition of a large chromophore (malachite green) to the 1-phosphate of (1,4,5)IP(3) only modestly reduced potency suggesting that similar analogues could be used to measure (1,4,5)IP(3) binding optically. These data provide the first structure-activity analyses of key IP(3) analogues using homogenous populations of each mammalian IP(3)R subtype. They demonstrate broadly similar structure-activity relationships for all mammalian IP(3)R subtypes and establish the potential utility of (1,4,5)IP(3) analogues with chromophores attached to the 1-position." @default.
• W2016387671 created "2016-06-24" @default.
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• W2016387671 date "2013-01-25" @default.
• W2016387671 modified "2023-09-28" @default.
• W2016387671 title "Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Analogues of IP3" @default.
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• W2016387671 doi "https://doi.org/10.1371/journal.pone.0054877" @default.
• W2016387671 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3556037" @default.
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