Blood 5-hydroxyindoles

A preliminary communication [420] reports low blood 5-hydroxyindoles in a group of children with behavioureJ disturbance and hyperactivity. The relevance of these findings to brain 5HT depends on the degree of reliability of the platelet as a model for central 5HT neurones [421]. It is worth noting however, that significant negative correlations are found between motor activity and brain 5HT in rats [349, 350, 422]. 

The blood-brain barrier foils most efforts to use the blood to measure the brain s chemistry, but researchers can get aroimd this obstacle by sampling cerebrospinal fluid (CSF). CSF is the fluid that circulates in the meninges of the brain and spinal cord and keeps the delicate tissues from getting rattled around and damaged in their hard, bony container. The brain makes CSF from blood, and certain metabolites get mixed in. One of these metabolites is 5-hydroxyindole acetaldehyde (5-FIIAA), a major metabolite of serotonin. Researchers who carefully puncture the meninges and extract a sample are rewarded with information concerning serotonin levels in the person s brain, as described below. 

HT is also metabolised by MAO to form 5-hydroxyindole aeetie acid (5-HIAA), which is actively transported across the blood-brain barrier out of the brain, in common with other low molecular weight organic acids (e.g. HVA uric acid). 

Yokogoshi, H., Kato, Y, Sagesaka, Y. M., Matsuura, T. T., Kakuda, T., and Takeuchi, N. 1995. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci. Biotechnol. Biochem. 59 615-18. 

Hydroxytryptamine is deaminated oxidatively to 5-hydroxyindole acetic acid. In addition, 5-hydroxytryptamine is catabolized in substantially smaller amounts by reduction to the corresponding alcohol, 5-hydroxytryptophol, (1868-70) is excreted in the free form and combined as the glucuronide or sulphate. 7V-Methylation of 5-hydroxytryptamine gives iV-methylsero-tonin, which can be methylated further to 7V, -dimethylserotonin (= bufotenine). The iV-methylation is catalysed by a relatively unspecific iV-methyltransferase. By acetylation of 5-hydroxytryptamine 7V-acetyl-serotonin is produced, which is an intermediary product in the course of the melatonin synthesis (= 5-methoxy-AT-acetylserotonin). The production of 5-methoxytryptamine, which we were able to demonstrate in normal human blood and urine, seems to occur fairly easily by deacetylation of melatonin, whereas a direct 0-methylation of serotonin to 5-methoxy-tryptamine, at least in vitro, takes place to a substantially smaller extent. ... 

Taking a concentration of 5-hydroxytryptamine of 0-05 jug/ml in the blood and an excretion of 3-6 mg per day of 5-hydroxyindole acetic acid as a basis, Erspamer estimated that the amount of 5-hydroxytryptamine contained in the total blood volume is metabolized every 2-3 hr. Heissel " found that C-marked serotonin in the thrombocytes of eleven healthy subjects had a half-life of 5-6 days. Sjoerdsma et found a pool of 2800 mg 5-hydroxytryptamine with a half-life of 5 days in a patient with a metastasized carcinoid of the small intestine after intravenous injections of C-marked hydroxytryptophane. Zucker et found a half-life of 1-7-2-8... 

In the course of malabsorption syndromes an increased excretion of 5-hydroxyindole acetic acid and of 3-indoleacetic acid " was observed. In the case of non-tropical sprue there was an increase of serotonin in the blood (1436) excretion of 5-hydroxyindole acetic acid. " " ... 

A massive phytochemical survey by the U.S. Department of Agriculture [610] has identified a number of useful sources of L-dopa, the most promising being cultivated velvet beans. However, the microbiological hydroxylation of A-formyl-L-tyrosine esters [436] can be duplicated chemically in excellent yield by the use of benzoyl peroxide in chloroform [611]. Reports state that L-dopa from Japanese sources is superior to that from the U.S.A. [612]. Suitability of patients for L-dopa therapy can be assessed by determination of homovanillic acid and 5-hydroxyindole-3-acetic acid levels before and after treatment with probenecid [613, 614]. This drug reduces the outflow of brain monoamine metabolites into the blood and provides an index of the degree of... 

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