PLATELET ACTIVATION

This review article describes the different receptors, second-messengers and mechanisms involved in platelet activation. Several platelet agonists have well-defined receptors at the platelet membrane of which a number are single polypeptides with 7 hydrophobic transmembrane domains. These receptors are connected, via GTP regulatory proteins, with cytoplasmic second-messenger-generating enzymes. Phospholipase C and adenylate cyclase are the two best-known enzymes, generating inositol triphosphate (IP3) and diacyl glycerol from phosphatidylinositol biphosphate and cyclic AMP from ATP respectively. The intraplatelet free calcium level, which is critical for the activation status of the platelet, is increased by IP3 and is lowered in the presence of rising cyclic AMP concentrations, Shape-change occurs with small increases in intraplatelet calcium, while aggregation and secretion of granules take place at higher calcium levels. The role of myosin and actin filaments and of transmembrane glycoproteins is further discussed.