Effect of dl-3-Pyridylalanie on Serotonin Concentration and Tryptophan-Serotonin Metabolizing Enzymes in Rats

抄録

A single administration of dl-3-pyridylalanine (3-PA, 100 mg/kg) significantly increased brain and serum serotonin (5-HT) concentrations without affecting the other tissue 5-HT concentrations (liver, kidney, spleen and small intestine) in male Wistar rats. The increase in brain 5-HT upon 3-PA administration was maintained for a long time (at least 96 h). Chronic administration of 3-PA (100 mg/kg/d) produced no change in brain 5-HT concentration as compared with that found in animals given a single dose of 3-PA. 3-PA decreased liver tryptophan pyrrolase (TP) activity and increased free tryptophan concentration in the serum. 3-PA hardly affected tryptophan 5-hydroxylase, 5-hydroxy-L-tryptophan (5-HTP) decarboxylase and monoamine oxidase (MAO) activities in the brain and liver. These findings suggest that the increase in brain 5-HT concentration upon administration of 3-PA occurs via the inhibition of liver TP, and an increase in free tryptophan concentration in the serum may be the causative factor for the increased brain 5-HT concentration. In contrast with 5-PA, 5-HTP (50 mg/kg, 10 mg/kg) increased the 5-HT concentrations of all tissues studied, and the brain 5-HT concentration fell to control (saline-treated) levels within several hours after the administration of 5-HTP (10 mg/kg, 6 h ; 50 mg/kg, 24 h). 5-HTP decreased brain tryptophan 5-hydroxylase and 5-HTP decarboxylase activities, and increased brain MAO and liver TP activities at 2 h after the administration.