Effect of aminophylline on tryptophan and other aromatic amino acids in plasma, brain and other tissues and on brain 5-hydroxytryptamine metabolism.

Abstract

1 Aminophylline and other methylxanthines increase brain tryptophan and hence 5-hydroxytryptamine turnover. The mechanism of this effect of aminophylline was investigated. 2 At lower doses (greater than 100 mg/kg i.p.) the brain tryptophan increase could be explained by the lipolytic action of the drug, i.e. increased plasma unesterified fatty acid freeing plasma tryptophan from protein binding so that it became available to the brain. 3 Plasma unesterified fatty acid did not increase when aminophylline (109 mg/kg i.p.) was given to nicotinamide-treated rats but as both plasma total and free tryptophan rose, a tryptophan increase in the brain still occurred. 4 The rise in brain tryptophan concentration following the injection of a higher dose of the drug (150 mg/kg i.p.) could no longer be explained by a rise of plasma free tryptophan as the ratio of brain tryptophan to plasma free tryptophan rose considerably. Plasma total tryptophan fell and the plasma insulin concentration rose. 5 The increase of brain tryptophan concentration after injection of 150 mg/kg aminophylline appeared specific for this amino acid as brain tyrosine and phenyllanine did not increase. However as their plasma concentrations fell the brain/plasma ratio for all three amino acids rose. 6 The higher dose of aminophylline increased the muscle concentration of tryptophan but that of tyrosine fell and that of phenylalanine remained unaltered. The liver concentrations were not affected. 7 The aminophylline-induced increase of the ratio of brain tryptophan of plasma free tryptophan no longer occurred when the drug was given to animals injected with the beta-adrenoreceptor blocking agent propranolol or the diabetogenic agent streptozotocin. 8 The changes in brain tryptophan upon aminophylline injection may be explained by (a) increased availability of plasma tryptophan to the brain due to increased lipolysis and (b) increased effectiveness of uptake of tryptophan by the brain due to increased insulin secretion.