Effect of administration of 5-hydroxytryptophan and an inhibitor of L-aromatic amino acid decarboxylase on glucose metabolism in rat brain.
The effect of 5-hydroxytryptophan (5-HTP)--the precursor of serotonin (5-hydroxytryptamine, 5-HT)--and of an inhibitor, N-(DL-seryl)-N'-(2,3,4-trihydroxybenzyl)hydrazine (Ro4-4602), of L-aromatic amino acid decarboxylase on the metabolism of glucose to amino acids in brain tissue was investigated. Labeled glucose (20 muCi, 0.24 mg in 0.2 ml 0.9% saline) was injected intravenously into fed rats pretreated with Ro4-4602 (50 mg/kg intraperitoneally) either alone or in combination with 5-HTP (30 mg/kg intravenously) or with the appropriate vehicle. After the injection of Ro4-4602 plus 5-HTP, the concentrations of 5-HT and 5-HTP in brain were increased, but the increase of 5-HTP was more pronounced and prolonged than the increase in 5-HT. This suggested that Ro4-4602 slightly inhibits the reaction of decarboxylation in the brain, although at the dose used the drug is usually considered to act only peripherally. After administration of Ro4-4602 alone or combined with 5-HTP, the concentration of glucose in plasma was not significantly increased. However, the concentration of glucose in brain was markedly increased with such treatments. The administration of Ro4-4602 alone or combined with 5-HTP reduced the flux of 14C from labeled glucose to amino acids in brain. The concentrations of amino acids in brain were little changed by these treatments.
D006916:5-Hydroxytryptophan / Q000032:analysis / Q000494:pharmacology*; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001545:Benserazide / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D012701:Serotonin / Q000032:analysis
D000596:Amino Acids; D001786:Blood Glucose; D005971:Glutamates; D006834:Hydrazines; D012701:Serotonin; D001545:Benserazide; D006916:5-Hydroxytryptophan; D005947:Glucose