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Evidence for the role of ammonia in the intracerebral transfer and metabolism of tryptophan
Author(s) -
Grippon Patrick,
le Poncin Lafitte Monique,
Boschat Michèle,
Wang Shwen,
Faure Grazyna,
Dutertre Dominique,
Opolon Pierre
Publication year - 1986
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840060424
Subject(s) - tryptophan , glutamine , serotonin , medicine , endocrinology , chemistry , blood–brain barrier , metabolism , tryptophan hydroxylase , efflux , amino acid , biochemistry , biology , central nervous system , serotonergic , receptor
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 NH 3 in the intracerebral transfer of tryptophan and serotonin metabolism, solutions containing either saline or NH 3 or tryptophan or NH 3 + 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 NH 3 infusion. NH 3 + 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 NH 3 infusion. When tryptophan and NH 3 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 NH 3 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 NH 3 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.