The effect of heparin on the inositol 1,4,5-trisphosphate receptor in rat liver microsomes Dependence on sulphate content and chain length

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Abstract

Heparin is known to inhibit the binding of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) to high-affinity binding sites and to inhibit Ins 1,4,5-P3-induced Ca2+ release from intracellular membrane-bound stores [(1987) J. Biol. Chem. 262, 12132-12136; (1987) FEBS Lett. 228, 57-59]. We have performed studies to clarify the structural requirements for this action of heparin in rat liver microsomes. Both N- and O-linked sulphate groups contribute to binding activity, since de-N-sulphated heparin was without effect on the Ins 1,4,5-P3 receptor whereas a polyxylan bearing only O-linked sulphates (pentosan polysulphate) was as active as heparin. Therefore, the density of negative charge contributed by sulphate groups is important for the binding of heparin. Heparins with high and low affinity for antithrombin III both inhibited Ins 1,4,5-P3 binding. There was a strong dependence on chain length, since binding activity decreased dramatically as the size of the heparin chain was reduced below that of 18-24 monosaccharide units. © 1989.

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APA

Tones, M. A., Bootman, M. D., Higgins, B. F., Lane, D. A., Pay, G. F., & Lindahl, U. (1989). The effect of heparin on the inositol 1,4,5-trisphosphate receptor in rat liver microsomes Dependence on sulphate content and chain length. FEBS Letters, 252(1–2), 105–108. https://doi.org/10.1016/0014-5793(89)80898-1

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