Platelets Serotonin

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. 

Chamba G, Lemoine P, Flachaire E, et al Increased serotonin platelet uptake after tianeptine administration in depressed patients. Biol Psychiatry 30 609-617, 1991... 

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

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

SERT, 5HTT (SLC6A4) 5HT = serotonin -1 CNS serotonergic neurons (emanate from raphe nuclei) platelets, smooth muscle, intestine ... 

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. 

Arora, R.C., and Meltzer, H.Y. In vitro effect of phencyclidine and other psychomotor stimulants on serotonin uptake in human platelets. Life Sci 27 1607-1613, 1980. 

Drugs that target other sites of platelet action include thromboxane synthetase inhibitors, serotonin or 5-hydroxytryptamine (5-HT2) receptor blockers, and thromboxane A2 receptor blockers, in addition to cyclooxygenase inhibitors and prostaglandin analogues. 

Rausch, 1., Fefferman, M., Ladisich-Rogers, D., Menard, M. Effect of nicotine on human blood platelet serotonin uptake and efflux. Prog. Neuropsychopharmacol. Biol. Psychiatry. 13 907, 1989. 

Patkar, A.A.G.R., Berrettini, W.H., Weinstein, S.P., Vergare, M.J., Leone, F.T. Differences in platelet serotonin transporter sites between African-American tobacco smokers and non-smokers. Psychopharmacology. 166 221, 2003. 

Blood platelets release ATP, ADP, serotonin, and other compounds and this plays an important role in thrombosis and hemostasy. To study the mechanism of the release, in vitro release of ATP was followed using the firefly luciferase luminescence method [124],... 

Serotonin is synthesized from tryptophan in two steps. Tryptophan is hydroxylated by tryptophan hydroxylase, and 5-hydroxytryptophan is decarboxylated to give serotonin. Most serotonin in the body is found in the enterochromaffin cells of the intestinal tract and the pineal gland. Platelets take up and store serotonin but do not synthesize it. 

To date, there have only been a limited number of studies directly examining PKC in bipolar disorders [77], Although undoubtedly an oversimplification, particulate (membrane) PKC is sometimes viewed as the more active form of PKC, and thus an examination of the subcellular partitioning of this enzyme can be used as an index of the degree of activation. Friedman etal. [78] investigated PKC activity and PKC translocation in response to serotonin in platelets obtained from bipolar-disorder patients before and during lithium treatment. They reported that the ratios of platelet-membrane-bound to cytosolic PKC activities were elevated in the manic patients. In addition, serotonin-elicited platelet PKC translocation was found to be enhanced in those patients. With respect to brain tissue, Wang and Friedman [74] measured PKC isozyme levels, activity and translocation in postmortem brain tissue from patients with bipolar disorder, and reported increased PKC activity and translocation in the brains of bipolar patients compared with controls, effects which were accompanied by elevated levels of selected PKC isozymes in cortices of bipolar disorder patients. 

Bermejo, N. et al., Platelet serotonin is a mediator potentially involved in anaphylactic reaction to neuromuscular blocking drugs, Br. J. Anaesth., 70, 322, 1993. 

The biogenic amines are the preferred substrates of MAO. The enzyme comes in two flavors, MAO-A and MAO-B, both of which, like FMO, rely on the redox properties of FAD for their oxidative machinery. The two isoforms share a sequence homology of approximately 70% (81) and are found in the outer mitochondrial membrane, but they differ in substrate selectivity and tissue distribution. In mammalian tissues MAO-A is located primarily in the placenta, gut, and liver, while MAO-B is predominant in the brain, liver, and platelets. MAO-A is selective for serotonin and norepinephrine and is selectively inhibited by the mechanism-based inhibitor clorgyline (82). MAO-B is selective for /1-phcncthylaminc and tryptamine, and it is selectively inhibited by the mechanism-based inhibitors, deprenyl and pargyline (82) (Fig. 4.32). Recently, both MAO-A (83) and MAO-B (84) were structurally characterized by x-ray crystallography. 

Furthermore, the myeloperoxidase systems can stimulate secretion of serotonin from platelets, histamine release from mast cells and the activation of latent collagenase and latent gelatinase of neutrophils. 

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