Activation of platelets

The various stimuli causing platelet activation act by signal transduction through receptors, ultimately increasing the free cytosolic Ca2+ level in platelets. Several calcium mobilization reactions interact with the receptors and regulate cytosolic free Ca2+. Adenosine triphosphate (ATP) is converted to cyclic adenosine monophosphate (cAMP) by the enzyme adenylate cyclase (AC); cAMP is broken down to AMP by the enzyme phosphodiesterase (PDE). When cAMP is elevated, for example by prostacyclin (PGI2) binding to a specific receptor and stimulating adenylate cyclase (AC), some Ca2+ is stored in the dense tubules, reducing cytosolic free Ca2+ and the level of platelet activation. Guanosine triphosphate (GTP) is converted to cGMP by guanylate cyclase (GC); cGMP is broken down by a PDE to produce guanosine monophosphate (GMP). When cGMP is elevated by stimulation of GC by NO, free cytosolic Ca2+ is reduced by inhibition from leaving the dense tubules. Thus, modulating free cytosolic Ca2+ can increase or decrease platelet activity. The final step in platelet-mediated thrombosis is the exposure/activation of the platelet glycoprotein IIb/IIIa fibrinogen receptor, which binds to fibrinogen to create a platelet aggregate.