Trace amines in hepatic encephalopathy.
In 1971 Fischer and Baldessarini proposed the hypothesis that hepatic encephalopathy (HE), a neuropsychiatric syndrome associated with hepatic dysfunction, could result from the direct decarboxylation of amino acids leading to trace amines such as tyramine and octopamine which could then act as false neurotransmitters. This was supported by the observation that the clinical symptoms of HE appeared to improve following treatment with L-Dopa, which cannot be metabolized to either of these trace amines. In addition to serum and urine levels of octopamine correlating roughly with the grade of clinical HE, levels of octopamine were also significantly increased in rat brain following coma induced by hepatic devascularization and in portacaval-shunted rats fed high aromatic amino acid content diets. This hypothesis was questioned, however, given the lack of observable adverse behavioural effects following treatments with octopamine. Finally, the equivocal results of a limited number of clinical trials (using L-Dopa) argued against a direct intervention by catecholamine-like trace amines in HE. An alternative hypothesis was advanced by Sourkes in 1978 implicating increased tryptophan metabolism as a factor in the etiology of HE. Hepatic dysfunction in humans alters CNS concentrations of tryptophan which correlate well with levels of the tryptamine metabolite indoleacetic acid (IAA). Furthermore, regional densities of [3H]tryptamine receptors in HE patient brain tissue are significantly decreased. These data support a pathophysiologic role for tryptophan and its neuroactive trace amine metabolite tryptamine in HE.
Mousseau
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DD
Neuroscience Research Unit, St-Luc Hospital, University of Montreal, Québec, Canada.
Butterworth
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RF
D000588:Amines / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000737:chemistry / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D006801:Humans; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000588:Amines; D002395:Catecholamines; D012701:Serotonin