Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Abstract

1 The effects on tryptophan distribution and metabolism of drugs altering plasma unesterified fatty acid (UFA) concentration were investigated in the rat. 2 UFA and plasma free (i.e. ultrafilterable) tryptophan altered in the same direction. 3 Catecholamines and L-DOPA increased both plasma UFA and free tryptophan. L-DOPA also increased brain tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) but decreased brain 5-hydroxytryptamine (5-HT). 4 Aminophylline increased plasma UFA and free tryptophan and also brain tryptophan, 5-HT and 5-HIAA. Food deprivation had qualitatively similar effects. 5 Insulin decreased plasma UFA and free tryptophan in both fed and food-deprived rats. However, while in fed rats these changes were associated with small decreases of brain indoles, in food-deprived animals small increases occurred. 6 Nicotinic acid had only small effects in fed rats but it opposed both the UFA and indole changes in food-deprived animals. Total plasma tryptophan increased in nicotinic acid treated, food-deprived rats. 7 There was a tendency towards inverse relations between changes of plasma free and total tryptophan. 8 The results suggest that drugs which influence plasma UFA through actions on cyclic AMP thereby alter the binding of tryptophan to plasma protein and that this leads to altered distribution and metabolism of tryptophan.

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

“…The percentage increases of brain tryptophan and 5-HIAA were only slightly higher as the dose of aminophylline increased and were comparable for both substances. As in earlier work (Curzon & Knott, 1974) …”

“…This fraction can be increased in conditions in which the plasma concentration of unesterified fatty acids (UFA) increases as these substances decrease the binding of tryptophan to albumin Curzon, Friedel & Knott, 1973;Curzon, Kantamaneni, Winch, RojasBueno, Murray-Lyon & Williams, 1973;Curzon & Knott, 1974;.…”

Tryptophan metabolism in alcoholism

“…As regards Trp binding, only about 10 % of circulating Trp exists in the free unbound state (though in equilibrium with the 90 % albumin-bound fraction) and therefore available for tissue uptake. Non-esterified fatty acids (NEFA) are the physiological displacers of albumin-bound Trp (Curzon & Knott, 1974), and it will be seen later (p. 132) that, in rats, acute ethanol administration increases Trp entry into the brain by increasing circulating NEFA concentration. Other agents increasing NEFA concentration include catecholamines, methylxanthines and clofibrate.…”

Rapid Effects of Environmental Disturbance on Rat Plasma Unesterified Fatty Acid and Tryptophan Concentrations and Their Prevention by Antilipolytic Drugs

“…In circumstances such as fasting and experimental hepatic coma (Curzon, Kantamaneni, Winch, Rojas-Bueno, Murray-Lyon & Williams, 1973) or following the administration of many drugs (Curzon & Knott, 1974;Knott & Curzon, 1975), the weakened binding of plasma tryptophan to albumin which results from an increase of plasma UFA appears to lead to increased brain tryptophan. Furthermore, a group of uninjected rats showed significant positive correlations between free trytophan in plasma and trytophan concentration in brain regions (Curzon, Kantamaneni, Fernando, Woods & Cavanagh, 1975 Another plasma amino acid, tyrosine, did not show similar changes to those of tryptophan.…”

“…Also, in stress situations increased plasma UFA may be associated with increase of brain tryptophan and 5-HT turnover, e.g. in the rat when deprived of food or immobilized Curzon & Knott, 1974). These are prolonged or extreme changes in the physical state of the animal.…”