Signal transducing mechanisms in platelets.
Platelets respond through discrete receptors to a number of physiological stimuli and foreign surfaces with a sequence of measurable responses: shape change, aggregation, secretion and arachidonate liberation. Three secretory responses are distinguished: release of substances from 1) dense granules (ADP, serotonin), 2) alpha-granules (coagulation factors, platelet-specific proteins, adhesive proteins) and 3) lysosomes (acid hydrolases). The liberated arachidonate is converted to prostaglandins and thromboxanes which, together with secreted ADP and close cell contact, will cause further platelet activation through "positive feedback" (autocrine stimulation). Some agonists are "weak" (ADP, vasopressin, platelet-activating factor) and depend on positive feedback to promote the full sequence of responses, while other agonists are "strong" (thrombin, collagen) and stimulate the entire response sequence without positive feedback. Most agonists appear to stimulate platelet responses via G-protein-dependent activation of phospholipase C, resulting in diesteratic hydrolysis of phosphatidylinositol-4,5-bisphosphate yielding inositol-1,4,5-trisphosphate and diacylglycerol. These are signal molecules which mobilize cytoplasmic Ca2+ and stimulate protein kinase C, respectively. Cytoplasmic Ca2+ will in turn activate protein phosphorylations which eventually lead to execution of the various responses while activation of protein kinase C appears to be linked to regulation of intracellular pH through Na+/H+ exchanger and to termination of the Ca(2+)-mediated signal processing. Other agonists (prostaglandins I2 and D2) counteract platelet stimulation through classical activation of adenylate cyclase.
Holmsen
H
H
Department of Biochemistry, University of Bergen, Norway.
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction
D011956:Receptors, Cell Surface; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium