5-Hydroxytryptophol: a metabolite of 5-hydroxytryptamine in rats

Kveder, S.; Iskrić, Sonja; Keglević, Dina

doi:10.1042/bj0850447

Cited by 79 publications

(25 citation statements)

References 8 publications

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“…Tryptophol was isolated as a tryptophan metabolite of yeast by Ehrlich in 1912 (2) and first identified from mammals as a tryptamine metabolite in rabbit liver (1). Subsequently, 5-hydroxytryptophol was identified as a serotonin (5-hydroxytryptamine) metabolite in rats (3,4), bovine pineals (5), and humans, both in vivo (6) and in brain tissue in vitro (7). Ethanolinduced modification of the metabolism of biogenic indole amines results in the increased production of tryptophol compounds, specifically 5-hydroxytryptophol (4,(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cornford¹,

Bocash²,

Braun³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Tryptophol (3-indole ethanol) is a compound which induces sleep, and is formed: (a) in the liver after disulfiram treatment, and (b) by the parasite in trypanosomal sleeping sickness. We prepared, purified, and characterized radiolabeled tryptophol for the purpose of defining its tissue distribution in animals. Tryptophol was found to be highly lipophilic, with an octanol: water partition coefficient of 29.8. Brain extraction, determined after intracarotid injection, was high (brain uptake index = 117+3.5%), and nonsaturable, suggesting the absence of a carrier system. After intravenous administration, tryptophol distribution to tissues correlated with relative blood flow. More than 85% of the radioactivity remaining in brain 2-5 min after intravenous injection co-migrated with tryptophol standards when analyzed by thin-layer chromatography. Other evidence suggested that tryptophol binds to serum and in vivo may be stripped from serum albumin and taken up by brain in a single capillary transit. Our study suggests that in states such as trypanosomal sleeping sickness or disulfiram treatment, remotely formed tryptophol gains ready access to brain (it is 100% cleared in a single capillary passage), and could thus cause somnolence.

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Section: Introductionmentioning

confidence: 99%

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cornford¹,

Bocash²,

Braun³

et al. 1979

J. Clin. Invest.

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confidence: 99%

The Formation of 5‐hydroxytryptophol in Brain in Vitro

Eccleston¹,

Moir²,

Reading³

et al. 1966

British Journal of Pharmacology and Chemotherapy

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Kveder, Iskric & Keglevic (1962) described the formation of 5-hydroxytryptophol from 5-hydroxytryptamine (5HT) in vivo in rats. The alcohol was isolated as conjugates from urine, and distinguished from 1'-N-acetyl 5-hydroxytryptamine by paper chromatography. Feldstein & Wong (1965) demonstrated the enzymatic conversion of 5HT to 5-hydroxytryptophol in rat liver. The alcohol appears also to be a major metabolite of the amine in platelets (Bartholini, Pletscher & Bruderer, 1964).The isolation of the alcohol from bovine pineal gland by McIsaac, Farrell, Taborsky & Taylor (1965) led us to attempt the synthesis of 5-hydroxytryptophol from 5HT in rat and subsequently human brain homogenates. METHODS Reagents5-hydroxytryptamine creatinine sulphate was obtained from Koch-Light Ltd., Colnbrook, and 5-hydroxyindolacetic acid from Roche Products, Hertfordshire. The authenticated sample of 5-hydroxytryptophol was a gift from the National Institutes of Health, Bethesda. Preparation of brain homogenatesWistar strain rats of either sex weighing 180-220 g were used. The animals were killed by decapitation and the brain was quickly taken out. After removal of the cerebral hemispheres and cerebellum the remainder of the brain was homogenized in 25 vol. 0.25M sucrose at 40; 1 ml. of the homogenate was preincubated in a metabolic shaking incubator for 15 min at 370. The reaction was started by the addition of 80 ,ug of 5HT in 1 ml. of 0.5M phosphate buffer, pH 7.4 (Feldstein & Wong, 1965), containing 500 ug of one of the pyridine nucleotide co-enzymes (nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide reduced (NADH2), nicotinamide adenine dinucleotide phosphate (NADP) and nicotinamide adenine dinucleotide phosphate reduced (NADPH2)). The reaction was stopped at varying intervals by the addition of 0.1 ml. conc. HCI. Human brain material obtained at necropsy from an adult female was examined in a manner similar to that described above-that is, samples of midbrain and cerebral cortex were dissected, homogenized in 25 vol. 0.25M sucrose at 40 and incubated with 5HT, etc.Estimation of 5-hydroxytryptophol, S-hydroxyindol-3-yl acetaldehyde and S-hydroxyindol-3-yl acetic acid (5HIAA) The analyses were a modification of the method reported by Feldstein & Wong (1965). Duplicate incubation mixtures were pooled and centrifuged at 3,000 rev/min for 7 min. After decantation the pH of the supernatant was adjusted to 7.4 (glass electrode) using SN NaOH, and passed through

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“…This metabolite was also found in the blood. No radioactive material was found which migrates in chromatographs as does N-acetyl-5-hydroxytryptamine (Mclsaac & Page, 1959), 5-hydroxytryptophol (Kveder, Iskric & Keglevic, 1962), 5-methoxytryptamine, melatonin (added as nonradioactive carriers), or to 5-hydroxytryptamine-O-sulphate (Airaksinen, 1963 Effect of monoamine oxidase inhibition. In Table 2 the levels of radioactivity found in various tissues 4 hr after the administration of [14C]5-HTP are compared for animals that did, or did not, receive previous treatment with the monoamine oxidase inhibitor JB 516.…”

Section: Resultsmentioning

confidence: 99%

Radioisotopic studies of the binding, exchange, and distribution of 5‐hydroxytryptamine synthesized from its radioactivity precursor

Gershon¹,

Ross²

1966

The Journal of Physiology

140

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SUMMARY1. The synthesis, distribution, storage, and subsequent metabolism of 5-hydroxytryptamine (5-HT) produced in mice from the administration of its radioactive precursor, 5-hydroxytryptophan, has been investigated to form the basis for a similar study to be conducted by radioautography.2. Intravenous injection of the radioactive material was found to be essential for significant uptake of radioactivity by tissue. The duration of the period during which radioactive material was available for uptake by the tissue was 2 hr.3. The relative distribution of radioactivity in individual organs was studied and the radioactive compounds present in each were identified and quantitatively assayed. No unrelated routes of metabolism of the labelled material were found and radioautographic results may be interpreted in terms of the metabolic picture which emerged.4. Radioactive 5-HT was bound in tissues in preference to both its precursor, and metabolite, 5-hydroxytryptamine-0-glucuronide, and the radioactive 5-HT produced in vivo after the injection of labelled 5-hydroxytryptophan probably entered and labelled the endogenous 5-HT pool.5. Fixatives prepared with buffer solutions made hypertonic by the addition of sucrose could rapidly and effectively halt the movement of radioactive 5-HT out of tissues and prevent its subsequent extraction during histological processing.6. It is concluded that localization of sites concerned with 5-HT metabolism by means of radioautography is feasible and the 5-HT so localized will probably reflect the physiological compartmentalization of the amine.Physiol. i86 29

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5-Hydroxytryptophol: a metabolite of 5-hydroxytryptamine in rats

Cited by 79 publications

References 8 publications

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

The Formation of 5‐hydroxytryptophol in Brain in Vitro

Radioisotopic studies of the binding, exchange, and distribution of 5‐hydroxytryptamine synthesized from its radioactivity precursor

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