Platelet activation.

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Abstract
Platelets are discoidal cytoplasmic particles that respond to a variety of stimuli by developing filopodia and rounding up (shape change), developing the ability to bind fibrinogen from the medium, and, with strong stimuli such as thrombin and PAF-acether, secreting the contents of several types of granules. Arachidonic acid is cleaved from phospholipids by phospholipase A2 and converted by the platelets to endoperoxides, and then to thromboxane A2. The bound dimeric fibrinogen molecules probably cause aggregation by forming bridges between platelets. Aggregation is reinforced by secreted fibrinogen and thrombospondin, which binds the platelets, and by thromboxane A2 and endoperoxides, as well as secreted ADP, which cause additional receptor-mediated activation. The responses to these stimuli are initiated when the agonists bind to specific receptors on the plasma membrane. Subsequent steps resemble those in other types of responsive cells: breakdown of phosphatidylinositol bisphosphate into diacylglycerol, a stimulator of protein kinase C, and inositol-1,4,5-trisphosphate, recently shown to be a potent calcium ionophore. The response of shape change results from increased cytoplasmic Ca2+ which permits phosphorylation of one of the light chains of myosin by a calcium-calmodulin-dependent kinase, with resulting enhanced actin-myosin interaction. Secretion is associated with phosphorylation of a 40,000 to 47,000 dalton protein by the diacylglycerol-activated protein kinase C. These recent findings have increased our understanding of the mechanisms of platelet activation, but much remains to be learned. How do agonist-receptor complexes influence PIP2 breakdown? Is this indeed the first step in activation? What mediates adhesion of platelets to the injured blood vessel wall? Does transduction of this stimulus occur by the same mechanism as transduction of commonly used soluble stimuli? What is the role of the phosphorylated 40-47 K protein in secretion? What change in GP IIb-IIIa promotes their ability to bind fibrinogen? What is the role of calcium-activated protease? Of the phosphorylation of actin-binding protein? Progress is being made rapidly, and these questions may be answered within a few years.