Evidence for the role of ammonia in the intracerebral transfer and metabolism of tryptophan

Authors

  • Dr. Patrick Grippon,

    Corresponding author
    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
    • Service d'Hepatogastroenterologie, Hǒpital de la Salpetrière, 47 boulevard de l'hǒpital, 75013 Paris, France
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  • Monique le Poncin Lafitte,

    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
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  • Michèle Boschat,

    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
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  • Shwen Wang,

    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
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  • Grazyna Faure,

    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
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  • Dominique Dutertre,

    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
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  • Pierre Opolon

    1. INSERM U-9, Hǒpital Saint Antoine, 75012 Paris, France and INRC VC, Centre Hospitalier de Bicětre, 94270 Le Kremlin Bicětre, France
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Abstract

After portacaval shunt in the rat, the transport of tryptophan and other neutral amino acids across the blood-brain barrier is enhanced. To determine the role of NH3 in the intracerebral transfer of tryptophan and serotonin metabolism, solutions containing either saline or NH3 or tryptophan or NH3 + tryptophan together were infused, respectively, into the internal carotid artery of rats in order to achieve blood levels similar to those observed after liver ischemia. After tryptophan infusion, a significant increase in the hypothalamic levels of tryptophan and 5-hydroxyindoleacetic acid was observed. A similar increment was found after NH3 infusion. NH3 + tryptophan infusion induced a significant increment in hypothalamic tryptophan and 5-hydroxyindoleacetic acid levels which were 2-fold greater than after tryptophan infusion. There was no significant change in 5-hydroxytryptamine levels in any of these experiments. Glutamine levels increased significantly after NH3 infusion. When tryptophan and NH3 were infused simultaneously, a significant reduction in glutamine levels occurred. These results cannot be explained by any modification of cerebral blood flow nor of the cerebral intratissular pH. Our data suggest that NH3 enhances the transfer of tryptophan across the blood-brain barrier and thus stimulates serotonin metabolism. The mechanism by which tryptophan transfer across the blood-brain barrier is facilated is unknown. The reduction in glutamine levels in the hypothalamus when NH3 and tryptophan are infused together may be explained either by an inhibition of synthesis or by an intratissular influx of neutral amino acids and an efflux of glutamine as suggested by James et al.

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