Probenecid-induced increase of 5-hydroxytryptamine synthesis in rat brain, as measured by formation of 5-hydroxytryptophan

Probenecid blocks the efflux of 5-hydroxyindole acetic acid (5-HIAA) from the central nervous system, and has therefore been used for turnover measurements of central 5-hydroxytryptamine (5-HT). This substance also elevates tryptophan (TP) levels in rat brain. In this investigation, the time courses...

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Bibliographic Details
Published in:Psychopharmacology 1979-01, Vol.60 (3), p.229-235
Main Authors: van Wijk, M, Sebens, J B, Korf, J
Format: Article
Language:English
Subjects:
5-Hydroxytryptophan - biosynthesis
Animals
Benserazide - pharmacology
Blood-Brain Barrier
Brain - metabolism
Brain Chemistry
Hydrazines - pharmacology
Hydroxyindoleacetic Acid - metabolism
Hydroxylation
Male
Probenecid - analysis
Probenecid - blood
Probenecid - pharmacology
Rats
Serotonin - biosynthesis
Stimulation, Chemical
Time Factors
Tryptophan - analysis
Tryptophan - blood
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Summary:Probenecid blocks the efflux of 5-hydroxyindole acetic acid (5-HIAA) from the central nervous system, and has therefore been used for turnover measurements of central 5-hydroxytryptamine (5-HT). This substance also elevates tryptophan (TP) levels in rat brain. In this investigation, the time courses of probenecid and TP levels in rat serum and brain after administration of probenecid were studied. Maximal levels of probenecid were reached within 15 min, followed by 50% decrease of serum TP and a 40% increase of brain TP. Brain levels of probenecid were about ten times lower than those in serum. Because TP level in brain is an important factor in the control of cerebral 5-HT synthesis, the effects of probenecid on 5-HT formation in rat brain were investigated. By means of the aromatic L-amino acid decarboxylase inhibitors Ro 4-4602 and NSD 1015, an enhancement of TP hydroxylation of about 35% was demonstrated. It was concluded that penetration of probenecid into the brain is very limited and that probenecid, in addition to blocking egress of 5-HIAA from the CNS, stimulates 5-HT synthesis.
ISSN:0033-3158
1432-2072
DOI:10.1007/BF00426660