The Formation of 5‐hydroxytryptophol in Brain in Vitro

Eccleston, D.; Moir, A. T. B.; Reading, H. W.; Ritchie, Isobel M.

doi:10.1111/j.1476-5381.1966.tb01905.x

Cited by 46 publications

(13 citation statements)

References 11 publications

(16 reference statements)

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“…A similar phenomenon was reported in the rat for metabolites of tyramine (Tacker et al, 1970). The above inability of ethanol to produce a reversal in the metabolism of biogenic amines in the brain is supported by reports on the effect of ethanol on 5-hydroxytryptamine metabolism in the whole rat brain (Tyce et al, 1970;Carlsson & Lindqvist, 1973) and in brain slices (Eccleston, Reading & Ritchie, 1969).…”

Section: Discussionsupporting

confidence: 65%

“…The brain metabolism of ,-hydroxylated biogenic amines (noradrenaline and octopamine) have been reported by several workers (Rutledge & Jonason, 1967;Breese, Chase & Kopin, 1969a,b;Eccleston et al, 1969) and predicted by a computer simulation approach to produce mostly the alcoholic metabolites (Turner, Illingworth & Tipton, 1974). Biogenic amines with no P-hydroxyl groups, on the other hand, were reported to form mostly the acidic metabolites.…”

Section: Discussionmentioning

confidence: 99%

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Brain Concentrations of Biogenic Amine Metabolites in Acutely Treated and Ethanol‐dependent Rats

Karoum

Wyatt

Majchrowicz

1976

British J Pharmacology

132

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Mass fragmentography was used to measure whole brain concentrations of some of the major metabolites of tyramine, octopamine, dopamine and noradrenaline in acutely treated and in ethanoldependent rats. Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p‐hydroxyphenylacetic and p‐hydroxymandelic acid (metabolites derived from tyramine and octopamine respectively). The effect on catecholamine metabolites was marked and therefore suggests that ethanol is selective in its effect on central metabolism of biogenic amines. Acute ethanol treatment significantly increased brain concentration of homovanillic acid (HVA), 3,4‐dihydroxyphenylacetic acid (DOPAC) and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG). Vanilmandelic acid (VMA) was not affected. All four metabolites (HVA, DOPAC, MHPG and VMA) were increased in the brains of rats rendered dependent on ethanol while still intoxicated (blood ethanol levels above 200 mg/dl). In ethanol‐dependent rats undergoing ethanol withdrawal syndrome (no ethanol present in blood), the brain concentrations of HVA and DOPAC were normal while those of MHPG and VMA continued to be elevated. From the decline in the concentrations of HVA and DOPAC after 50 mg pargyline/kg in control rats and rats acutely treated with ethanol, it was concluded that ethanol has no effect on the transport of phenolic acids across the blood brain barrier. No reversal in the metabolism of catecholamines from an oxidative to a reductive pathway, analogous to that produced by ethanol in the periphery, could be established in the brain. The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Brain Concentrations of Biogenic Amine Metabolites in Acutely Treated and Ethanol‐dependent Rats

Karoum

Wyatt

Majchrowicz

1976

British J Pharmacology

132

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“…In rat (Table 2) and human (Feldstein, Williamson & Tedeschi, unpublished) brain homogenates, we have found that 5-HIAA formation was moderately stimulated by NAD+ and to a lesser extent by NADP+. The quality of the NAD+ may explain the difference between our results and those obtained by Eccleston et al (1966), because enzymic activity was dependent on the source of the coenzyme (Table 3). The NAD+ used in our studies was rated greater than 99% pure by the company and had maximal activity available.…”

Section: Discussioncontrasting

confidence: 87%

“…The quality of the NAD+ may explain the difference between our results and those obtained by Eccleston et al (1966), because enzymic activity was dependent on the source of the coenzyme (Table 3). The NAD+ used in our studies was rated greater than 99% pure by the company and had maximal activity available.…”

Section: Discussioncontrasting

confidence: 56%

5‐Hydroxytryptamine metabolism in rat brain and liver homogenates

Feldstein¹,

Williamson²

1968

British J Pharmacology

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1. The metabolism of 5-hydroxyindoleacetaldehyde derived from 5-hydroxytryptamine incubated with tissue homogenates was studied as an indicator of aldehyde dehydrogenase and alcohol dehydrogenase activities. 2. In liver and brain from rats, there were indications of the presence of one or more aldehyde dehydrogenases which were stimulated by NAD+ to a greater extent than by NADP+. 3. In liver from rats, there were indications of the presence of one or more alcohol dehydrogenases, which were stimulated by NADH to a greater extent than by NADPH. 4. In brain from rats, there were indications of the presence of one or more alcohol dehydrogenases which were stimulated by NADPH to a greater extent than by NADH.Eccleston, Moir, Reading & Ritchie (1966) reported that 5-hydroxytryptamine (5-HT) was converted to 5-hydroxytryptophol by way of 5-hydroxyindoleacetaldehyde in rat and human brain homogenates. These investigators found that the conversion in brain was effected by an alcohol dehydrogenase which depended on NADPH (Eccleston, Moir, Reading & Ritchie, 1966) rather than NADH as in liver (Kveder, Iskric & Keglevic, 1962; Feldstein & Wong, 1965a, b). It was reported also that the conversion of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) by way of 5-hydroxyindoleacetaldehyde in rat brain homogenates was more effective in the presence of NADP+ than NAD+ (Eccleston, Moir, Reading & Ritchie, 1966), although another investigator (Deitrich, 1966) found that NAD+ was the more effective. The effects of the coenzymes on 5-HT metabolism in both rat liver and brain homogenates were re-investigated and the results reported herein. MethodsMale rats, Sprague-Dawley descendants, [150][151][152][153][154][155][156][157][158][159][160][161][162][163][164][165]

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“…5-Hydroxytryptophol and its conjugates have been identified as normal metabolites in human urine and human and rat brain homogenates (10,11). Ethanol consumption shifts tryptophan metabolism away from the oxidation metabolite, 11, toward the reduced metabolite, V, as a result of the increased ratio of reduced to unreduced nucleotide cofactors effected by ethanol metabolism (12,13).…”

Section: Introductionmentioning

confidence: 99%