Serotonin platelet activation

Histamine Serotonin Platelet-activating factor (PAF) Eicosanoids (various prostaglandins and leukotrienes) C3a, C4a, and C5a from the complement system Bradykinin and fibrin split products from the coagulation system... 

Platelets originate by budding off from multinucleate precursor cells, the megakaryocytes. As the smallest formed element of blood (dia. 1 -4 pm), they can be activated by various stimuli. Activation entails an alteration in shape and secretion of a series of highly active substances, including serotonin, platelet activating factor (PAF), ADP, and thromboxane A2. In turn, all of these can activate other platelets, which explains the explosive nature of the process. 

Release of active substances such as serotonin, platelet-activating factor (PAF), ADP, and thromboxane A2. All these substances activate other platelets. 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

The autacoids comprise histamine, serotonin, angiotensin, neurotensin, NO (nitric oxide), kinins, platelet-activating factor, endothelins and the four families of traditional eicosanoids - the leukotrienes and three types of prostanoids i.e. prostaglandins, prostacyclins, and thromboxanes. Several other natural occurring molecules are sometimes called eicos-anoid, including the hepoxilins, resolvins, isofurans, isoprostanes, lipoxins, epoxyeicosatrienoic acids (EETs) and some endocannabinoids. However, not... 

Note. fMLP = formylmethionylleucylphenylalanin 5-HT = serotonin NS = not significant PAF = platelet activating factor PHA = phytohemagglutinin RBCs = red blood cells. 

Some studies have shown increased risks of violent death and depression in subjects with reduced serum cholesterol concentrations. Serum and membrane cholesterol concentrations, the microviscosity of erythrocyte membranes, and platelet serotonin uptake have been determined in 17 patients with hypercholesterolemia (21). There was a significant increase in serotonin transporter activity only during the first month of simvastatin therapy. This suggests that within this period some patients could be vulnerable to depression, violence, or suicide. This is an important paper, in that it explains why mood disorders are not regularly seen in clinical trials with statins, as has been summarized in a recent review (3). 

Apprill P, Schmitz JM, Campbell WB et al. (1985) Cyclic blood flow variations induced by platelet-activating factor in stenosed canine coronary arteries despite inhibition of thromboxane synthetase, serotonin receptors, and a-adrenergic receptors. Circulation 72 397-405... 

PAF stimulates platelet aggregation and serotonin secretion in a stracturally specific maimer. For example, lyso-PAF, the inactive stmctural analog has no platelet activating... 

Serotonin binds to the platelet 5-HTj receptor coupled to PLC via a G protein. The human serotonin receptor has been cloned and have the usual seven transmembrane domain form (Saltzman et al., 1991). Serotonin is rapidly taken up by passive diffusion and by a high affinity eneigy-dependent carrier, and is released upon platelet activation by secretion ftom the dense granules (Pletscher, 1987). 

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