Effects of hydrocortisone and immobilization on tryptophan metabolism in brain and liver of rats of different ages.
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Biomedical subjects
Publications and source records attributed to G Curzon.
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1 The psychotropic effects of a single oral dose of (--)-tryptophan (5 g) in human volunteers were investigated using a series of physiological and psychological tests. 2 Self-ratings of mood showed increase in drowsiness but no euphoria was detected. 3 Severe initial nausea occurred and headache increased; other bodily symptoms were unaffected. 4 Trptophan caused increased activity in the slow wavebands of the EEG but did not alter the other physiological measures. 5 The levels of total and free tryptophan in the plasma increased 8 and 20 fold respectively to peak levels 2 h after ingestion.
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1 Changes of plasma unesterified fatty acid (UFA) and tryptophan concentration in group-housed rats following removal of their cage-mates and the effects of antilipolytic drugs on these changes were investigated. 2 Removal of group-housed 24 h fasted rats but not fed rats from cages resulted in increased plasma UFA concentration in the remaining rats which was associated with significant increases of the proportion of free tryptophan but significant falls of total tryptophan concentration. These rapid changes were not associated with brain tryptophan changes. Plasma tyrosine concentration was unaffected. 3 The fall of plasma tryptophan did not appear to be due to passage into red cells as erythrocyte tryptophan concentration remained unchanged. 4 Plasma UFA concentrations correlated positively and significantly with corticosterone concentrations which were also increased following removal of cage-mates. 5 Plasma UFA increases and tryptophan changes in the fasting rats were both prevented by nicotinic acid or propranolol. Corticosterone concentration was increased by nicotinic acid but unaffected by propranolol. 6 The possible importance of these rapid changes of plasma tryptophan and of their prevention by antilipolytic drugs is discussed.
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Addition of linoleic acid to rat plasma caused increased uptake of radioactive tryptophan by incubated brain slices. Addition of competing amino acids within the physiological range of their concentrations had negligible effect. Rat midbrain tryptophan concentration in vivo correlated significantly with plasma free tryptophan. These results are consistent with previous work indicating the importance of plasma free tryptophan as a determinant of brain tryptophan concentration.
Although CSF HVA is derived from brain DA metabolism the value of its determination as an index of brain DA turnover and dopaminergic activity is limited, as other factors can affect CSF concentrations. These include the partitioning of HVA between different routes of elimination from the brain, the rates of transport from CSF to blood and from the lateral ventricle to the lumbar sac, CSF space volumes, and methodologic problems. The uses and limitations of CSF HVA determination is illustrated by findings in Parkinson's disease, Huntington's chorea, motor neuron disease, disseminated sclerosis, and hepatic coma. Finally, preliminary results on the effect on CSF HVA of the DA agonist CB 154 are described.
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Patients with stupor or coma from fulminant hepatic failure were found to have high cerebrospinal fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA), metabolites of dopamine and serotonin respectively. Excessive amounts of their precursors-phenylalanine and tyrosine and free tryptophan-were found in the patients' plasma. Methionine, which participates in dopamine degradation, was also much increased. Similar disturbances were found in patients suffering an acute exacerbation of chronic encephalopathy. These abnormalities would be consistent with other evidence of an increased turnover of serotonin and possibly dopamine in the brain during hepatic encephalopathy.
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