Platelet 5-hydroxytryptamine

Racke, K., Schworer, H., Simson, G. Effects of cigarette smoking or ingestion of nicotine on platelet 5-hydroxytryptamine (5-HT) levels in smokers and non-smokers. Clin. Invest. 70 201, 1992. 

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. 

Platelet 5-Hydroxytryptamine Lipoxygenase metabolites Platelet-activating factor Thromboxane A2... 

Anand M, Gopal K, Agrawal C, et al. 1986. Endosulfan induced inhibition of 3H 5-hydroxytryptamine uptake in platelets. Toxicol Lett 32 203-208. 

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. 

Kimura, Y., Okuda, H., and Arichi, S. (1988). Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets. /. Pharm. Pharmacol. 40, 838-843. 

Certain foods can trigger a migraine attack by effects on neurotransmitter release or metabolism in the brain. For example, a number of foods contain tryptamine which is known to cause release of other amines (dopamine, noradrenaline and 5-hydroxytryptamine) from both nerve terminals and platelets. This release could initiate the sequence of events that results in the migraine attack. Elimination of such foods from the diet can decrease the number of headaches. Compounds that discourage platelet aggregation (e.g. aspirin) may prevent such attacks. 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Serotonin (5-hydroxytryptamine, or 5HT) is present in the brain as well as in the periphery. In humans, about 90% of the total serotonin in the body is in enterochro-maffin cells in the gastrointestinal tract the remaining 10% occurs primarily in the platelets and brain. The physiological significance of the vast amounts of serotonin constantly synthesized and metabolized in the periphery still remains an enigma. Brain serotonin has been implicated as a potential neurotransmitter in the mediation of a wide variety of phenomena (see Actions). 

In Section 1.3, the general effects of fluorine substitution on drug activity and selectivity have been treated. As seen frequently with other enzymatic reactions, introduction of fluorine can have dramatic effects on the properties of substrates and inhibitors of MAOs [26]. For example, preliminary studies indicated that fluorination of 5-hydroxytryptamine in the 6- or the 4,6-positions (3,4) causes this predominantly MAO A substrate to be metabolized significantly by platelet MAO B [27]. Although no direct evidence was obtained, this may be caused by increased lipophilicity introduced by fluorine substitution. 

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... 

Hydroxytryptamine is widely distributed in plant and animal tissues, mast cells, platelets, the enterochromaffin cells located throughout the gastrointestinal tract, and in certain regions of the brain. It is also present in the venoms and stings. Some fruits such as bananas, pineapples, tomatoes and plums contain considerable amount of 5-HT. 

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

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. 

A molecule such as cyclic AMP, cyclic GMP or phosphatidylinositol that regulates intracellular processes in response to an extracellular signal. Uncontrolled or paroxysmal brain activity that is usually expressed through the motor system. Antidepressants such as fluoxetine and fluvoxamine that show specificity in inhibiting the uptake of 5-hydroxytryptamine into platelets or brain tissue in vitro and in vivo. 

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

Krishnamurti S, Jose S, and Kakkar W. (1987). Effect of phorbol 12-myristate 13-acetate (PMA). (HI agonsit-induced arachidonate release and 3-hydroxytryptamine secreation in human platelets Dependence of effects cm agonist type and time of incubation with PMA. Biochim. Biophys. Acta 927, 429-436. 

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. 

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. 

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