5-hydroxyindol acetic acid

The possible effects of hallucinogens on central monoaminergic neurons were first explored by Freedman (34), who discovered that a single injection of LSD increases 5-HT levels in the rat brain, whereas its inactive congener BOL fails to affect brain 5-HT. Since this change is associated with a decrease in the concentration of the main metabolite of 5-HT, 5-hydroxyindole acetic acid (5-HIAA) (Fig. 1), Rosecrans et al. (98) postulated that LSD administration in... 

Also, harmala alkaloids create effects on monoamine turnover. Postnatal rats administered harmaline (shortly before birth) have elevations in brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG), but decreases in the dopamine and serotonin metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) (Okonmah et al. 

Table 1. Significant increase (P<0.05, t-test) in dihydroxyphenyl acetic acid (DOPAC) and 5-hydroxyindol acetic acid (5-HIAA) in the mouse hypothalamus following treatment of mice with Agaricus muscarius 12 through the oral route. No significant change in the level of dopamine (DA) and serotonin (5 HT) was observed. Data from Sc Cult 56 134-135 (1990) reproduced with author s permission.

It therefore appears that the main action of reserpine is to produce a biochemical change so that the cells no longer retain a high concentration of serotonin. In other words, the binding of serotonin is prevented. Thus, after the administration of 5-hydroxytryptophan (a precursor of serotonin) to rabbits pretreated with reserpine, serotonin is rapidly formed but remains in a free form. Presumably, free serotonin, before it is metabolized to 5-hydroxyindole acetic acid by amine... 

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-hydroxyindole 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. 

List of Abbreviations Ach, acetylcholine AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid CNS, central nervous system COMT, catechol-O-methyltransferase DA, dopamine DRP-2, dihy-dropyrimidinase-related protein 2 DSM, diagnostic and statistical manual of mental disorders GNAS1, guanine nucleotide-binding protein (G-protein) alpha stimulating activity polypeptide 1 5-HIAA, 5-hydroxyindole acetic acid 5-FIT, serotonin (5-hydroxytryptamine) MAO, monoamine oxidase MHPG, 3-methoxy-4-hydroxyphenylglycol NE, norepinephrine NMDA, N-methyl-D-aspartate PCP, phencyclidine SSRI, selective serotonin reuptake inhibitor SDS, schedule for the deficit syndrome... 

Serotonin (5-hydroxytryptamine, 5-HT) is synthesized from the essential amino acid tryptophan. It is a biogenic amine belonging to the indole family. 5-HT is broken-down by MAO and ultimately metabolized to 5-hydroxyindole acetic acid (5-HIAA). In the brain, the 5-HT afferents originate in the raphe nuclei and project to the striatum, thalamus, hippocampus, amygdala, and cortex. 

HK 5-ASA 5-fflAA 5-HT 5- HT 6- OHDA 8-OHdG yc 3-hydroxykynurenine 5-aminosalicychc acid 5-hydroxyindole acetic acid 5- hydroxy hyptophan 5 -hydroxy hyp t amine 6- hydoxydopamine 8-hydroxy-2 -deoxyguanosine common y-chain ... 

Jerome et al. (J2) found that urinary excretion of 5-hydroxyindole-acetic acid, indoleacetic acid, and xanthurenic acid was less in 15 mongoloids than in 16 normal children. An oral dose of 30 mg/kg of L-trypto-phan produced an increased excretion of these compounds, the increase being in the same proportion in the mongoloids as in the normal. Excretion of kynurenine is at the same level in both groups and is increased after the loading test. 

Most tryptamine molecules are metabolized by the enzyme monoamine oxidase (MAO). MAO actually occurs in two different forms, MAO-A and MAO-B, which have preferences for different neurotransmitter molecules. MAO-A oxidizes the terminal amine of the tryptamines to an imine. This imine then undergoes nonenzymatic hydrolysis to an aldehyde that is subsequently converted to a carboxylic acid by a second enzyme, aldehyde dehydrogenase. The result is the conversion of the tryptamine into an acidic molecule, called an indole-3-acetic acid, which lacks psychoactivity. DMT is converted into indole acetic acid, whereas serotonin is converted into 5-hydroxyindole acetic acid (5-HIAA), and psilocin is converted into 4-hydroxy indole acetic acid. 

Garcia, A. Heinanen, M. Jimenez, L.M. Barbas, C. Direct measurement of homovaniUic, vaniUylmandehc and 5-hydroxyindole acetic acids in urine by capillary electrophoresis. J. Chromatogr., A 2000, 871, 341-350. Vanholder, R. de Smet, R. Lameire, N. Protein bound uremic solutes The forgotten toxins. Kidney Inter., Suppl. 2001, 78, S266-S270. 

The sedative effect of palmatine on locomotor activity and concentration of monoamine in rats was studied via behavioral and biochemical methods. Palmatine was shown to enhance the hypomotility induced by a-methyl-p-tyrosine, reserpine, and 5-hydroxytryptophan, but reduced the hypermotility produced by L-dopa plus benserazide and p-chlorophenylalanine. In addition, the alkaloid significantly decreased the concentration of dopamine and homovanillic acid in the cortex and the concentration of serotonin in the brain stem, but increased the concentration of 5-HT in the cortex and 5-hydroxyindole acetic acid in the brain stem. These results suggest that the sedative action associated with palmatine may be related to the decrease in catecholamine concentration in the cortex and serotonin in the brain stem, and the increase in the concentration of 5-HT in the cortex [309],... 

Coulometric detectors are also used. When placed in a series, such detectors are used to detect and quantify coeluting compounds that differ in their half-wave potentials (the potential at half-signal maximum) by at least 60 mV. These detectors are extremely selective and sensitive, with reasonably wide linear response ranges. They are used in the clinical laboratory for the analysis of metanephrines, vanil-lymandelic acid, homovaniUic acid, and 5-hydroxyindole acetic acid in human urine without extensive sample preparation. 

Warburton R, Keevil B. Urinary 5-hydroxyindole-acetic acid by high-performance fiquid chromatography with electrochemical detection. Ann Clin Biochem 1997 34 (Pt 4) 424-6. 

Org 6582 (12) was found to be a strong, long lasting blocker of 5-HT uptake, five times chlorimipramine, with no apparent effect on NE uptake systems.13 Compound L2 also caused a decrease in 5-HT turnover and lowered brain 5-HIAA (5-hydroxyindole acetic acid). 

Not only is methamphetamine administration toxic to the dopaminergic system, but the serotonergic system in the various brain areas is also altered. Hotchkiss and Gibb (1980) reported that methamphetamine, administered as described above, decreased tryptophan hydroxylase (TPH) activity in the serotonergic nerve terminal of rat brain and spinal cord. Similarly, the content of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were also severely depressed. In contrast to the effects in the dopaminergic system, these serotonergic parameters were decreased by methamphetamine within 15 minutes after a single dose... 

Disposition - It is possible that one mechanism for the disposition of the endogenously produced amine is by diffusion, which could be followed by re-uptake by nerve endings (or by other material in tissues) as has been shown with norepinephrine. But as yet there is no evidence for such a cycle for HT, although, as noted above, brain and its particulate fractions have the capacity for uptake. A main catabolic pathway for HT is oxidative deamination by monoamine oxidase to form 5-hy-droxyindoleacetaldehyde, most of which is converted to 5-hydroxyindole-acetic acid (HIAA) by aldehyde dehydrogenase and NAD S, 56 relatively small portion is reduced to 5-hydroxytryptophol by alcohol dehydrogenase and NADH " Monoamine oxidase, which, like... 

Gessa et al.1 were the first to demonstrate that the acute administration of an amino acid mixture containing all of the essential amino acids, except tryptophan, caused a rapid fall in plasma free and total tryptophan in rats. Furthermore, this effect was associated with a parallel depletion in brain tryptophan, serotonin, and 5-hydroxyindole acetic acid in rats.2 These early studies opened the way for subsequent studies, using acute tryptophan depletion by feeding a tryptophan-free amino acid mixture, a simple, specific, and nontoxic method, to delete brain serotonin and thus provide a tool for clarifying the physiological role of serotonin in the central nervous system. 

AgRP Agouti-related gene product 5-HIAA 5-Hydroxyindole acetic acid... 

Hydroxy"5-methoxytryptamine produces an increase in exploratory behavior in animals, but not significant from controls. No effect on serotonin norepinephrine brief decrease in 5-hydroxyindole acetic acid (5-HIAA). (Maickei 1978)... 

Urinary indole profile Larger excretion of 5-hydroxyindole acetic acid, 5-hydroxy tryptamine, and kynurenine are consistently present but indican is absent 48,135, 229... 

In many instances, such as in cancer, it is important to analyze a single or very few cells rather than homogenizing the whole tissue. Small capillaries of 10pm in diameter have been used to study the level of some metabolites in single cells, e.g., catecholamines, 5-hydroxyindole acetic acid including the level of the enzyme lactate dehydrogenase. However, cell introduction into the capillary and lyses is not an easy task. Eurthermore, this analysis requires the use of very sensitive detection. 

The indoleamines The indole of greatest significance in human metabolism is serotonin (5-hydro-xytryptamine (5-HT)) which is synthesized from tryptophan and metabolized by the monoamine oxidase system to 5-hydroxyindole acetic acid (5-HIAA). Serotonin is believed to play a significant role in maintenance of mood and many antidepressant drugs act via the serotoninergic receptor system. 

Fig. 1 Chromatograms of a standard solution of monoamine transmitters and their metabolites at (A) a poly(para-aminobenzoic acid) modified electrode and (B) a bare glassy carbon electrode. (1) Norepinephrine, (2) epinephrine, (3) dopamine, (4) 3,4-dihydroxyphenol acetic acid, (5) serotonin, (6) 5-hydroxyindole acetic acid, and (7) homovanillic acid. Source From Study on the effect of electromagnetic impulse on neurotransmitter metabolism in nerve cells by high performance liquid chromatography-electrochemical detection coupled with microdialysis, in Anal. Biochem. ...

Dubas and Hrdina (1978) and Dubas et al. (1978) reported that endogenous levels of 5-hydroxytryptamine were decreased in cortex and hypothalamus, and levels of its metabolite 5-hydroxyindole acetic acid were decreased in cortex, midbrain and hypothalamus. 

Dugandzic, M., Stankovic, B., Milovanovic, L. and Koricanac, Z. (1973). Urinary excretion of 5-hydroxyindole acetic acid in lead-exposed persons. Ark. Hig. Rada ToxsikoL, 24, 37... 

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