Regulation of glycoprotein IIB/IIIA exposure on platelets stimulated with alpha-thrombin.
Previous studies have shown that binding sites for fibrinogen on platelets stimulated with platelet-activating factor (PAF), adenosine diphosphate or epinephrine rapidly close in the absence of fibrinogen. In the present study we investigated whether alpha-thrombin induced similar changes in the glycoprotein (GP) IIB/IIIA-complex. Whereas 80% of binding sites exposed by PAF closed within 30 minutes (22 degrees C), alpha-thrombin (0.1 U/mL) triggered long-lasting exposure of binding sites for [125I]-fibrinogen and [125I]-fibronectin. Even removal of alpha-thrombin with an excess of hirudin failed to close the binding sites. Similar to PAF, alpha-thrombin-exposed sites rapidly closed after addition of the protein kinase C inhibitor staurosporine (1 mumol/L) or dibutyryl cyclic adenosine monophosphate (250 mumol/L). In contrast, prostacyclin (PGI2, 10 ng/mL), which induced rapid closure of binding sites in platelets stimulated with PAF, failed to close the sites in alpha-thrombin-treated platelets. Removal of alpha-thrombin from the platelets restored the PGI2-sensitivity. These data indicate that a short interaction between alpha-thrombin and platelets triggers long-lasting exposure of GPIIB/IIIA. Furthermore, as long as alpha-thrombin remains bound to the platelets, agonists that activate the PGI2-receptor are unable to close GPIIB/IIIA.
van Willigen
G
G
Department of Hematology, University Hospital Utrecht, The Netherlands.
Akkerman
J W
JW
D000470:Alkaloids / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine; D013917:Thrombin / Q000494:pharmacology*
D000470:Alkaloids; D005353:Fibronectins; D006629:Hirudins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D003994:Bucladesine; D005340:Fibrinogen; D011464:Epoprostenol; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine