The occupancy of glycoprotein IIb-IIIa complex modulates thrombin activation of human platelets.
Platelet membrane glycoprotein (GP IIb-IIIa), besides its activity as adhesive protein receptor, displays a number of properties supporting its involvement in the mechanisms of transduction of the activation signal. Recently we have observed that GP IIb-IIIa ligands, mostly fibrinogen, inhibit Ca2+ movement and cytoskeleton reorganization caused by mild platelet activation. These findings led us to investigate the effect of GP IIb-IIIa ligands on agonist-induced platelet responses, with particular attention to the two major messenger generating systems, involving the activation of phospholipase C and the inhibition of cAMP production. In this paper we demonstrate that the occupancy of the major adhesive protein receptor on the platelet surface modulates the phosphatidylinositol cycle decreasing the amount of IP3, IP2 and IP produced after mild platelet activation as well as the pattern of protein phosphorylation. The platelet cAMP content of activated platelets was also affected and kept higher when evaluated under the same experimental conditions. Our data provide evidence for a role of fibrinogen binding in regulating the degree of activation of circulating platelets.
Sinigaglia
F
F
Department of Biochemistry, Faculty of Sciences, University of Pavia, Italy.
Torti
M
M
Ramaschi
G
G
Balduini
C
C
D001792:Blood Platelets / Q000502:physiology*; D000242:Cyclic AMP / Q000097:blood; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000097:blood; D007700:Kinetics; D010710:Phosphates / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism / Q000502:physiology*
D007295:Inositol Phosphates; D010710:Phosphates; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D000242:Cyclic AMP; D013917:Thrombin