BINDING OF HEPARIN AND COMPOUND-Y TO ENDOTHELIAL-CELLS STIMULATES THESYNTHESIS OF AN ANTITHROMBOTIC HEPARAN-SULFATE PROTEOGLYCAN

The mechanism by which heparin and antithrombotic agents, including a cyclic octaphenolsulfonic acid (compound Y), stimulate the synthesis o f an antithrombotic heparan sulfate by endothelial cells in culture wa s investigated. Compound Y increases the amount of heparan sulfate fro m the cell surface and secreted to the medium by endothelial cells by three-fold. Binding experiments have shown saturation of the endotheli al cell receptors at a concentration of 0.16 mu M for heparin and 2.7 mu M for compound Y. The kinetic binding constants (Ks) for compound Y and heparin were 1,333 nM and 42 nM, respectively. It was also shown that both compounds bind to the same receptors. The Scatchard plots in dicated that 1,319 nmoles compound Y and 35 nmoles heparin bound per m icrogram cell protein, indicating that 40-fold more molecules of compo und Y bound to the receptors when compared to heparin. No significant internalization Of the compounds was observed.