Serotonin 5-Hydroxy tryptamine

Fig. 30-27). The fact that L-tryptophan has some antidepressant activity, but L-dopa does not, was one clue that a low concentration of serotonin (5-hydroxy-tryptamine) might be responsible for depression. Excessive formation of histamine1099 and decreased formation of tyramine and octopamine1100 have also been suggested as causes of depression. 

Kurrasch-Orbaugh DM, Watts VJ, Barker EL, Nichols DE. Serotonin 5-hydroxy-tryptamine(2A) receptor-coupled phospholipase C and phospholipase A(2) signaling pathways have different receptor reserves. J Pharmacol Exp Ther 2003 304 229-237. 

Launay JM, Herve P, Peoc h K, et al. Function of the serotonin 5-hydroxy-tryptamine 2B receptor in pulmonary hypertension. Nat Med 2002 8 1129-1135. 

Serotoninergic 5-HT3 receptors (cationic) transduce the effects of serotonin (5-hydroxy tryptamine, 5-HT), altogether with others 5-HT receptors which are GPCR. Selective 5-HT3 antagonists, like ondansetron and analogs, are antiemetics used during cancer therapy. 

Serotonin (5-hydroxy- tryptamine) Cell bodies in midbrain and pons project to all levels 5-HT, buspirone is a partial agonist Inhibitory t K conductance, i cAMP... 

Hydroxy tryptamine, or serotonin, is a neurotransmitter in the central nervous system (CNS). The nerve-cell bodies of the major serotoninergic neurones are in the midline raphe nuclei of the rostral pons, and ascending fibers innervate the basal ganglia, hypothalamus, thalamus, hippocampus, limbic forebrain, and areas of the cerebral cortex. The serotoninergic system plays an important role in the control of mood and behavior, motor activity, hunger, thermoregulation, sleep, certain hallucinatory states, and some neuro-endocrine mechanisms. 

Fozard JR. The development and early clinical evaluation of serotonin 5-HT3 receptor antagonists. In Fozard JR, ed., The Peripheral Actions of 5-Hydroxy-tryptamine. Oxford Oxford University Press, 1989 355-376. 

Histamine is synthesized from the amino acid histidine by simple decarboxylation catalysed by histidine decarboxylase. Serotonin is synthesized primarily in platelets, the gastro-intestinal (GI) tract and the brain from the indolyl amino acid tryptophan tryptophan —> 5-hydroxytryptophan [via tryptophan hydroxylase + tetrahydrobiopterin] —> 5-hydroxy-tryptamine (serotonin) [via 5-hydroxytryptophan decarboxylase]. 

HT1A-R, metabotropic 5-hydroxy-tryptamine (serotonin) receptor 5-HT1-R, metabotropic 5-hydroxy-tryptamine (serotonin) receptor 5HT2-R, metabotropic 5-hydroxy-tryptamine (serotonin) receptor 5HT3-R, ionotropic 5-hydroxytryptamine receptor... 

LSD acts on several sites in the central nervous system. It is a nonselective serotonin, or 5-hydroxy-tryptamine (5-HT) agonist on both presynaptic and postsynaptic receptor sites. The 5-HT2a receptor agonism is implicated in the modulation of hallucinations. In addition to the role of serotonin in causing hallucinations, other neurotransmitters, including glutamate and Di and D2 dopamine receptors, are implicated yet, their role remains elusive. 

Serotonin Agonists. Dysfunction of neurotransmission mediated by 5-hydroxy-tryptamine (5-HT serotonin) occurs in the basal ganglia of patients with PD, and excessive serotonergictransmission may contribute to dyskinesias associated with dopaminergic treatments (186). 5-HT receptors are expressed presynaptically on 5-HT terminals, where they limit serotonin release as autore-ceptors (187). Their activation should decrease 5-HT release and perhaps alleviate dopaminergic dyskinesias in PD (188). Because 5-HTia receptor stimulation can reverse par-... 

In 1950, Schurr et al.1 determined the amino add concentrations in various tissues of the rat. When these data were used to calculate tissue/plasma ratios, it became apparent that the relative availability of plasma tryptophan to tissues was much less than that of the other amino acids. In 1957, McMe-nemy et al.2 described a unique property of tryptophan It was the only amino acid in human plasma that was largely bound to protein. This attribute, specifically the ratio of free to bound tryptophan in the blood, has much physiological significance. For example, only the small free fraction of plasma tryptophan has access to the brain. Factors that influence the equilibrium between free and bound tryptophan in the plasma have been considered to alter the availability of tryptophan to the brain, where it has special importance as a precursor of the neurotransmitter 5-hydroxy-tryptamine (serotonin).3 5 Tryptophan differs from other amino acids in that its concentration in plasma of rats increases (30 to 40%) after fasting, after insulin administration, or after consuming a carbohydrate meal.6... 

The hydroxylation of tryptophan produces 5-hydroxytryptophan, which can then be decarboxylated, catalyzed by tryptophan decarboxylase, a PALP-requiring enzyme, to 5-hydroxy tryptamine, also known as serotonin. Serotonin is an important compound in normal brain function and tranquility. Therefore, any disturbance of tryptophan metabolism via this pathway can lead to mental disturbances. Serotonin can be destroyed by the enzyme monoamine oxidase (a flavo protein), which catalyzes the formation of ammonia and 5-hydroxyindole acetaldehyde in an irreversible reaction. The aldehyde is rapidly oxidized enzymatically, utilizing NAD+ to form 5-hydroxy indoleacetate, which is then usually excreted. The formation and turnover of serotonin can be estimated by 5-hydroxy indoleacetate output in the urine. 

Frovatriptan is a serotonin 5-HT,-receptor agonist, which selectively agonizes 5-hydroxy-tryptamine, (5-HT,b/id) receptor, inhibiting excessive dilation of extracerebral and intracranial arteries in migraine. It is indicated in acute treatment of migraine attacks with or without aura m adults. 

Biosynthesis Like other aromatic amino acids, e.g., Phe and Tyr, Trp is formed on the shikimic acid pathway. There is a branching point at chorismic acid one branch leads to Phe and Tyr, the other to Trp choris-mic acid - anthranilic acid (anthranilic acid synthase, EC 4.1.3.27)- A-(5 -0-phosphoribosyl)-anthranilic acid (anthranilic acid phosphoribosyl transferase, EC 2.4.2.18)- 1 -o-carboxyphenylamino-1 -deoxyribu-lose 5-phosphate [A-(5 -phosphoribosyl)anthranilic acid isomerase]- indole-3-glycerol phosphate (in-dole-3-glycerol phosphate synthase, EC 4.1.1.48) - indole (tryptophan synthase, EC 4.2.1,20)+serine - Trp. Many biologically active indole compounds are derived from Trp, e. g., 5-hydroxytryptophan, 5-hydroxy-tryptamine ( serotonin), and melatonin as well as many indole alkaloids. 

In our 1-hydroxyindole hypothesis, we had predicted that 5-hydroxy-tryptamines (serotonins) and 5-hydroxytryptophans were supplied from the 1-hydroxytryptophan residues in the tryptophans-containing peptides by the mediation of acids that are hnked with the TCA (Kreb s) cycle [2,5-7]. 

Bernheimer, H., Birkmayer, W. and Hornykiewicz, O., Verteilung des 5-Hydroxy-tryptamins (Serotonin) im Gehim des Menschen und sein Verhalten bei Patienten mit Parkinson-Syndrom, Klin. Wschr. 39 (20), 1056 (1961). 

Udenfriend, S., Weissbach, H. and Clark, C. T., The estimation of 5-hydroxy-tryptamine (serotonin) in biological tissues, J, Biol. Chem. 215, 337 (1955). 

ScHiEVELBEiN, H., Werle, E. and Jacoby, W., tJber die Freisetzung von 5-Hydroxy-tryptamin (Serotonin) aus Geweben durch Nikotin, Naturwiss. 48, 602 (1961). 

An intermediate in the conversion of tryptophan to 5-hydroxy tryptamine (serotonin). In some cases of carcinoid syndrome it i excreted in large amounts in the urine, even though the 5 hydroxyindoleacetic acid excretion may be normal. This i thought to be because the cells lack the decarboxylase whicl converts 5-hydroxytryptophan to 5-hydroxytryptamine. 

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