A Study of Proposed Determinants of Brain Tryptophan Concentration in Rats After Portocaval Anastomosis or Sham Operation

Abstract

liver dysfunction was produced in rats by surgical portocaval anastomosis (PCA), and the time-course of changes in brain tryptophan and 5-HT metabolism studied in relation to plasma changes possibly influencing brain tryptophan concentration.Brain tryptophan and 5-hydroxyindolylacetic acid (5-HIAA) levels were increased greatly and maximally on the day after PCA and remained high. 5-HT changes were less marked but had a similar time-course. Plasma total tryptophan was little changed but plasma free tryptophan was raised. The latter change showed a similar time-course to that of brain tryptophan but was not large enough to account completely for it. Sham operation was followed by significant but transient increases in plasma free tryptophan, brain tryptophan and 5-HIAA but these were much smaller than after PCA.Brain tryptophan did not correlate with plasma total tryptophan either in control or PCA rats but it correlated significantly with plasma free tryptophan in both groups. However brain levels were much higher in PCA rats than in controls with similar plasma free tryptophan levels at all times from the first day after operation. The increase of brain tryptophan in anastomosed rats not accounted for by plasma free tryptophan was explained neither by insulin changes nor by an increase of the insulin/glucagon ratio nor by changes in plasma concentrations of those amino acids which compete with tryptophan for entry into brain. The results therefore indicate an unknown influence on brain tryptophan concentration in PCA rats. As tyrosine changes in brain and plasma after PCA were very similar to those of tryptophan this influence may not be specific to tryptophan. Results suggest that under the conditions used brain tryptophan concentrations of both PCA and control rats are more influenced by changes of plasma free tryptophan concentration than by changes of plasma concentrations of competing amino acids.. 4~. J . P / t ! , .~i~/ . 221, 1629-1639. 483-487.

The Acute Effects of Reserpine and NSD-1015 on the Brain Serotonin Synthesis Rate Measured by an Autoradiographic Method

“…These results indicated that the decrease in 5-HT synthesis rate in reserpine-treated rats found in the present work could not be a consequence of a disturbance in the uptake of plasma tryptophan into the brain. It was reported earlier that the increase in plasmafree tryptophan increases the brain 5-HT synthesis rate (Bloxam and Curzon 1978;Diksic et al 1991). In the present work we found that NSD-1015 (a commonly used inhibitor of decarboxylase activity) induces a timedependent increase in the plasma-free tryptophan that could influence the transport of tryptophan from plasma into the brain and consequently increase 5-HT synthesis.…”

A New Method to Measure Brain Serotonin Synthesis in vivo. I. Theory and Basic Data for a Biological Model

“…3 Table 1). Because of this, the absolute value of the synthesis rates presented in Table 5 and calculated with the LC estimated from ratios given in Table 1 (Bloxam and Curzon, 1978;Anderson, 1979). Tryptophan also competes with other branched chain and aromatic amino acids for the same carrier (Pardridge, 1977;Yuwiler et aI., 1977).…”

“…(This has been confirmed in separate experiments to be pub lished.) It has been suggested that this ratio is the most important single factor determining brain tryp tophan concentration (Fernstrom and Wurtman, 1972;Bloxam and Curzon, 1978;Anderson, 1979) and is a determining factor in the rate of serotonin synthesis. On this basis, the plasma free tryptophan concentration was used in the calculation with Eq.…”

Tryptophan metabolism in liver cirrhosis: Influence of oral antibiotics on neuropsychiatric symptoms.

“…The hyperinsulinemia occurring concomitantly facilitates the decrease in branched chain amino acids, leading to increase in transfer of aromatic amino acids into the brain (Munro et al 1975). Meanwhile, Bloxam and Curzon (1978) reported that brain Trp concentration was more influenced by changes in plasma free Trp concentration than by changes in plasma concentration of competing amino acids. While Smith and Prockop (1962) observed various neuropsychiatric signs and symptoms following oral administration of Trp (30-90 mg/kg), Greenwood et al (1974) were unable to detect any overt mood change by intravenous infusion of Trp (75-100 mg/kg).…”