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- W2057469685 abstract "Alfa-trinositol (or D-myo-inositol 1,2,6-trisphosphate) was recently found to, e.g., inhibit agonist-induced vasoconstriction and display antiinflammatory properties. However, its mechanism of action is unknown, although effects on Ca2+ fluxes, perhaps by interfering with endogenous inositol phosphate(s), have been suggested. Here we describe the existence of specific [3H]alpha-trinositol binding sites and compare these with binding sites for naturally occurring inositol phosphates. For this purpose we developed a tritiated analog of alpha-trinositol and used it in a centrifugation binding assay on extensively washed membranes from rat tissues. The degree of specific [3H] alpha-trinositol binding was markedly increased as a result of the many wash steps, indicating the existence of endogenous binding inhibitor(s). A single population of [3H] alpha-trinositol binding sites, displaying a KD of 159 nM and a Bmax of 71 pmol/mg protein, was present in cardiac membranes assayed at pH 7.4. Similar binding site densities were detected also in liver > lung > brain. The relative density of [3H] alpha-trinositol sites in cardiac membranes was 8-fold higher than [3H]Ins(1,4,5)P3 but 2-fold and 4-fold lower than [3H]Ins(1,3,4,5)P4 and [3H]InsP6 binding sites, respectively. Competition binding studies indicated the ability of Ins(1,3,4,5)P4 and InsP6, but not Ins(1,4,5)P3, to potently displace [3H] alpha-trinositol binding. Conversely, unlabelled alpha-trinositol showed relatively low potency vs. [3H]InsP6, but the novel inositol phosphate was virtually equipotent with Ins(1,3,4,5)P4 in inhibiting [3H]Ins(1,3,4,5)P4 binding. Finally, analyses of binding at different pH and ionic conditions revealed differences between alpha-trinositol and the three other previously studied inositol phosphates, although distinct similarities between alpha-trinositol and Ins(1,3,4,5)P4 were again observed." @default.
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- W2057469685 date "1994-06-01" @default.
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- W2057469685 title "Characterization of specific binding sites for α-trinositol (d-myo-inositol 1,2,6-trisphosphate) in rat tissues" @default.
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- W2057469685 doi "https://doi.org/10.1016/0922-4106(94)90119-8" @default.
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