Conjugated 3,4 dihydroxy phenyl acetic acid (DOPAC) in human and monkey cerebrospinal fluid and rat brain and the effects of probenecid treatment

Abstract

Gas chromatography-mass spectrometry (GC-MS) was used to measure 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in cerebrospinal fluid from humans and monkeys and in rat caudate nuclei. DOPAC was found to be present mainly in conjugated form. In human lumbar CSF the average concentration of total DOPAC before probenecid treatment was 1.48 ± 0.31 ng/ml; after probenecid it increased to 15.06 ± 3.17 ng/ml. This increase was mainly due to conjugated DOPAC but increases in free DOPAC also occurred. There is a relatively greater accumulation of DOPAC than of HVA, suggesting that in human CSF conjugated DOPAC may have a faster turnover rate than HVA. In monkey, ventricular CSF contained higher concentrations of DOPAC and HVA than did lumbar CSF. In rat brain, treatment with probenecid caused increases in DOPAC, HVA and their conjugates. These results suggest that DOPAC is conjugated in brain and that both compounds are removed from brain and CSF by a probenecid-sensitive acid transport system in the same manner as is HVA.