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

Lane, David A.¹  Tones, Michael A.²  Pay, Graham F.²  Higgins, Bernard F.²  Bootman, Martin D.²  Lindahl, Ulf³ 

[1] Department of Haematology, Charing Cross and Westminser Hospital Medical School, Fulham Palace Rd, London SW15 5PN, England;Thrombosis Research Unit, Ciba-Geigy Pharmaceuticals, Wimblehurst Road, Horsham RH12 4AB, England;Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

关键词: Heparin;    Fragmin;    Pentosan polysulfate;    Inositol 1;    4;    5-trisphosphate receptor;    (Rat liver microsome);   

DOI  :  10.1016/0014-5793(89)80898-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown