Mechanism of potentiation of antithrombin III [AT-III] inhibition by sulfated xylans.
Anticoagulant properties of three sulfated compounds prepared from xylans isolated from corn cobs, larchwood and oatspelts were compared with heparin and sodium pentosan polysulfate (SP-54) by studying their effects on activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using pooled normal human plasma. These compounds were more effective than SP-54 in delaying coagulation by all the three procedures while oatspelts xylan sulfate was as effective as heparin in inhibiting APTT and PT and more effective than heparin in inhibiting TT on a molar basis. The sulfated xylans were more effective than heparin or SP-54 in potentiating the AT-III inhibition of amidolysis of H-D-Phe-Pip-Arg-pNa (S-2238) by thrombin (IIa) or amidolysis of Bz-Ile-Glu-Gly-Arg-pNa (S-2222) by Xa. Study of the high affinity binding of the xylan sulfates to AT-III-Sepharose column showed that the amount of the xylan sulfate recovered in the eluates from this peak was greatly increased with an increase in molecular weight (MW). A buffered mixture of IIa, AT-III and dansylarginine N-(3-ethyl-1,5-pentanediyl) amide (DAPA) was used to study the inactivation of IIa by AT-III. Larchwood xylan sulfate (2-10 micrograms) was found to accelerate this inactivation which was neutralized by human platelet factor 4 (PF4). The results also suggested an interaction between larchwood xylan sulfate and IIa which may potentiate an interaction between AT-III and IIa.
D000925:Anticoagulants; D000990:Antithrombin III / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D004357:Drug Synergism; D002523:Edible Grain / Q000032:analysis; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013431:Sulfates / Q000494:pharmacology; D014934:Wood; D014990:Xylans / Q000302:isolation & purification / Q000494:pharmacology*; D003313:Zea mays / Q000032:analysis
D000925:Anticoagulants; D011134:Polysaccharides; D013431:Sulfates; D014990:Xylans; D010426:Pentosan Sulfuric Polyester; D000990:Antithrombin III; D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa