Albumin binding and brain uptake of 6-fluoro-dl-tryptophan: competition with l-tryptophan

Chanut, Evelyne; Zini, Roland; Trouvin, Jean‐Hugues; Riant, P; Tillement, J P; Jacquot, C.

doi:10.1016/0006-2952(92)90112-v

Cited by 9 publications

(9 citation statements)

References 12 publications

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“…First, the decrease in Trp levels in the presence of AM-Trp in both light and dark groups might result from competition between Trp and AM-Trp for neuronal uptake, as described previously for another competitive substrate of TPH, 6-fluoro-DL-tryptophan (Chanut et al 1992). After Trp treatment, the increase in Trp level observed only in the dark group may be explained by several processes, such as an increase in protein degradation, a higher Trp uptake or a reduced catabolism.…”

Section: Discussionmentioning

confidence: 80%

Serotonin synthesis and its light–dark variation in the rat retina

Chanut

Nguyen‐Legros²,

Labarthe

et al. 2002

Journal of Neurochemistry

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Retinal circadian rhythms are driven by an intrinsic oscillator, using chemical signals such as melatonin, secreted by photoreceptor cells. The purpose of the present work was to identify the origin of serotonin, the precursor of melatonin, in the retina of adult rat, where no immunoreactivity for serotonin or tryptophan hydroxylase had ever been detected. To demonstrate local synthesis of serotonin in the rat retina, substrates of tryptophan hydroxylase, the first limiting enzyme in the serotonin pathway, have been used. Tryptophan, in the presence of an inhibitor of aromatic amino acid decarboxylase, enhanced 5-hydroxytryptophan levels, whereas a-methyltryptophan, a competitive substrate inhibitor, was hydroxylated into a-methyl-5-hydroxytryptophan. Tryptophan hydroxylase substrate concentration was higher in the dark period than in the light period, and formation of hydroxylated compounds was increased. The presence of tryptophan hydroxylase mRNA in the rat retina was confirmed by RT-PCR. Taken together, the results support the local synthesis of serotonin by tryptophan hydroxylation, this metabolic pathway being required more critically when 5-HT is used for melatonin synthesis.

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Section: Discussionmentioning

confidence: 80%

Serotonin synthesis and its light–dark variation in the rat retina

Chanut

Nguyen‐Legros²,

Labarthe

et al. 2002

Journal of Neurochemistry

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“…In Fig. 1, the emission spectra of BSA are shown in the presence of various concentrations of tinidazole (1). As can be seen, the fluorescence intensity of BSA decreased linearly (inset; R ¼ 0.9981) with increasing concentration of 1, with a significant red shift upon drug addition, which indicates that tinidazole quenches the inner fluorescence of BSA upon complexation.…”

mentioning

confidence: 89%

“…It is active against protozoa and anaerobic bacteria, and is used like its congener metronidazole ( ¼ 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol; 2) against various infections [11]. Tinidazole (1) has been reported to be hydrolyzed quantitatively under alkaline conditions to 2-methyl-5-nitro-1H-imidazole (3), and under photolytic conditions, the drug yields intermediate, rearrangement, and degradation products [12].…”

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confidence: 99%

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Spectroscopic Analysis of the Binding Interaction Between Tinidazole and Bovine Serum Albumin (BSA)

Shi

Cao

Ren

et al. 2007

Chemistry & Biodiversity

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The interaction between bovine serum albumin (BSA) and tinidazole (Tindamax; 1) in aqueous solution was investigated in detail by means of UV/VIS and fluorescence spectroscopy, as well as through resonance light-scattering (RLS) spectroscopy. The apparent binding constant and number of binding sites were determined at three different temperatures, as well as the average binding distances between 1 and the nearest amino acid residue(s) of BSA, as analyzed by means of Förster's theory of non-radiation energy transfer. Compound 1 was found to quench the inner fluorescence of BSA by forming a tight 1:1 aggregate, based on both static quenching and non-radiation energy transfer. The entropy change upon complexation was positive, and the enthalpy change was negative, indicating that the observed spontaneous binding is mainly driven by electrostatic interactions.

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“…Based on preliminary findings in rats (18), this is thought to be an underlying principle of the ATD challenge procedure introduced by Young et al because of reduced substrate availability for brain 5-HT synthesis with regard to reduced plasma TRP levels. Moreover, ATD makes use of the outlined competitive substrate inhibition, resulting in a diminished uptake of endogenous TRP into the central nervous system at L-1 (19–23). Specifically, the administered AAs compete with endogenous TRP at L-1 for uptake into the central nervous system.…”

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confidence: 99%

Dietary tryptophan depletion in humans using a simplified two amino acid formula – a pilot study

Linden

Helmbold

Kempf

et al. 2016

Food & Nutrition Research

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BackgroundAcute tryptophan depletion (ATD) is a well-established dietary method in translational brain research used to briefly lower central nervous serotonin (5-hydroxytryptamine (5-HT)) synthesis. A simplified two amino acid ATD formula (ATDPHE/LEU) was developed while reducing the overall amount of amino acids (AAs), with the objective of administration especially in children and adolescents in future studies.ObjectiveThis study investigated tryptophan (TRP) influx rates across the blood-brain barrier (BBB) after dietary ATDPHE/LEU administration relative to the ATD Moja-De protocol that has been established for use in children and adolescents.DesignSeventy-two healthy adults (50% females) were randomized into four groups and administered ATD Moja-De, its TRP-balanced control condition (BAL), ATDPHE/LEU, or its respective control mixture (BALPHE/LEU) in a counterbalanced, double-blind, between-subjects design. Blood samples were collected at baseline and at hourly intervals for 6 h after AA intake. Questionnaires about mood, taste, and challenge tolerance were completed at fixed time points.ResultsBoth challenge mixtures significantly reduced central nervous TRP influx as calculated by Michaelis–Menten kinetics relative to baseline and the respective control conditions with only mild and comparable side effects. A greater decline in TRP influx over the BBB after ATDPHE/LEU administration when compared with ATD Moja-De was detected without group effects for taste, challenge tolerance, and mood. There was unintended initial short increase in plasma TRP concentrations observed after ATDPHE/LEU intake, and a possible redistribution between free and protein-bound TRP triggered by protein synthesis stimulated by the ingested AAs may account for this finding. Moreover, a decline in TRP influx after BALPHE/LEU administration over a 6-h period was observed, and the large amount of PHE in the BALPHE/LEU mixture may be a possible explanation for this particular phenomenon, which could have led to an unexpected increase in displacement of TRP at the BBB in this control condition.ConclusionsThis pilot study provides preliminary evidence for the possibility of lowering TRP influx as calculated by Michaelis–Menten kinetics into the brain by using a simplified ATD protocol in humans. The simplified composition of only two AAs, the lower overall AA amount, and the appropriate tolerance are characteristics of the newly developed ATDPHE/LEU protocol. Future studies focusing on the effects of the ATDPHE/LEU protocol and its respective control condition on CSF 5-HIAA concentrations, as well as neurochemical studies in rodents, are needed to further validate this newly developed AA mixture before definite conclusions about its usability in ATD-related research in humans, its specificity, and additional effects can be made.

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Albumin binding and brain uptake of 6-fluoro-dl-tryptophan: competition with l-tryptophan

Cited by 9 publications

References 12 publications

Serotonin synthesis and its light–dark variation in the rat retina

Serotonin synthesis and its light–dark variation in the rat retina

Spectroscopic Analysis of the Binding Interaction Between Tinidazole and Bovine Serum Albumin (BSA)

Dietary tryptophan depletion in humans using a simplified two amino acid formula – a pilot study

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