Blood platelets, 5-hydroxytryptamine

Serotonin (4.109, 5-hydroxytryptamine, 5-HT) is a central neurotransmitter that is also found peripherally in the intestinal mucosa and in blood platelets, where its role is incompletely elucidated it even occurs in plants such as bananas. Although there is an enormous literature on the biochemistry and pharmacology of serotonin, our knowledge of its biological role remains somewhat fragmented. The diverse physiological effects of 5-HT influence the cardiovascular system, the cerebrovascular system, the digestive... 

Tuomisto J, Tukiainen E. Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature 1976 262 596-598. 

PLETSCHER a. The 5-hydroxytryptamine qrstem of blood platelets ] ysiology and pathophysiology. Int J Cardiol 14 177-188,1987. 

Serotonin (5-hydroxytryptamine, 5-HT) is synthesised in enterochromaffin cells, largely in the gut, and also extensively taken up into blood platelets from which it is released to have vascular effects. It has complex effects on the cardiovascular system, varying with the vascular bed and its physiological state it generally constricts arterioles and veins and induces blood platelet aggregation it stimulates intestinal and bronchial smooth muscle. Carcinoid tumours secrete serotonin and symptoms may be benefited by serotonin antagonists, e.g. cyproheptadine, methysergide and sometimes by octreotide (see Index). It is a neurotransmitter in the brain. 

Tryptophan appears to be converted to a larger number of metabolites than any of the other amino acids. The degradation of tryptophan in animals occurs mainly in two pathways, I and II (Figure 4.1). The first major pathway (I), initiated by the action of tryptophan dioxygenase, involves oxidation of tryptophan to N - fc > r my I ky n urenine and the formation of a series of intermediates and byproducts, most of which appear in varying amounts in the urine, the sum of which accounts for the total metabolism of tryptophan, approximately. The second pathway (II) involves hydroxylation of tryptophan to 5-hydroxytryptophan and decarboxylation of this compound to 5-hydroxytryptamine (serotonin), a potent vasoconstrictor found particularly in the brain, intestinal tissues, blood platelets, and mast cells. A small percentage (3%) of dietary tryptophan is metabolized via the pathway (III) to indoleacetic acid. Other minor pathways also exist in animal tissues. 

In blood platelets approximately 60% of the ADP + ATP is contained in granules together with serotonin (5-hydroxytryptamine). These adenine nucleotides are relatively inert metabolically, as incubation of platelets with radioactive precursors does not lead to their labeling, whereas non-particulate nucleotides readily become highly labeled (see references 28, 29). 

Serotonin (5-hydroxytryptamine, 5-HT) occurs in the intestinal wall, where it regulates motility and secretion in blood platelets, where it modulates platelet aggregation and vascular blood flow and in the CNS, where it acts as a neurotransmitter in areas of the midbrain. At least seven different receptors for serotonin have been characterized, which mediate a wide variety of different physiological effects. Depression and anxiety are thought to be the result of actions on 5-HTia receptors in the brain limbic system. Following release from neurons by a depolarizing action potential at central synapses, the activity of 5-HT is terminated by neuronal reuptake. This is performed by a synaptic membrane amine transporter protein, specific for 5-HT, which also co-transports sodium and chloride ions to repolarize the neuronal membrane. 

The ability of feverfew extracts to inhibit release of serotonin (5-hydroxytryptamine) from blood platelets has been suggested as mechanism of action in treatment of... 

Serotonin, also called 5-hydroxytryptamine, is synthesized and stored at several sites in the body (Figure 21.18). By far the largest amount of serotonin is found in cells of the intestinal mucosa. Smaller amounts occur in platelets and in the central nervous system. Serotonin is synthesized from tryptophan, which is hydroxy-lated in a reaction analogous to that catalyzed by phenylalanine hydroxylase. The product, 5-hydroxytryptophan, is decarboxylated to serotonin. Serotonin has multiple physiologic roles, including pain perception, affective disorders, and regulation of sleep, temperature, and blood pressure. 

Conversely, proaggregatory agents induce this mechanism of adhesion (e.g. thromboxane. ADP, 5-HT and PAF). 5-HT (serotonin) stimulates platelet aggregation and is. as its name implies, a vasoconstrictor in many blood vessels. It is actively taken up into platelets, and released on insult. See 5-HYDROXYTRYPTAMINE RECEPTOR AGONISTS. 

Ortiz J, Artigas F. Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood different effects of clomipramine and fluoxetine. Br J Pharmacol 1992 105 941-6. 

The vasoconstrictor action of shed blood tested by perfusion of the rabbit ear is markedly decreased by heparin and this was known long before the identification of the vasoconstrictor activity as serotonin (5-hydroxytryp-tamine). Heparin inhibits the release of both 5-hydroxytryptamine and a polypeptide from platelets into plasma, and in vitro there is mutual antagonism between heparin and 5-hydroxytryptamine . Heparin effectively antagonizes the effect of serotonin on pulmonary vascular bed and bronchial wall musculature and prevents the symptoms of 5-HT release in pulmonary embolism, in the cardiopulmonary by-pass, in experimental burn injuries and in carcinoid tumour. 

Serotonin (5-hydroxytryptamine, enteramine) occurs widely in both animals, and plants. It arises from tryptophan by hydroxylation in the 5-position and subsequent decarboxylation (the reverse sequence, proceeding via tryptamine, has been excluded). It affects the blood pressure and, among other effects, migrates from the platelets into the serum during blood clotting. Furthermore, it occurs in the intestinal mucosa, where it promotes peristalsis. Finally, it has been found in the central nervous system and appears to function in several psychic phenomena in a manner not yet understood. 

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