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

Gordon, Edna K.; Markey, Sanford P.; Sherman, Raymond L.; Kopin, Irwin J.

doi:10.1016/0024-3205(76)90206-x

Cited by 62 publications

(18 citation statements)

References 12 publications

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“…As far as conjugates are concerned, only a few reports are available for conjugated HVA in rat brain (striatum, olfactory tubercles, brain minus striatum, anterior part of brain) (Gordon et al, 1976;Swahn and Wiesd, 1976;Elchisak et al, 1977;Bacwoulos et al, 1979;Dedek et al, 1979;Sarna et al, 1984). Our present data are consistent with previous values.…”

Section: Brain Conjugates At Basal Statesupporting

confidence: 95%

“…However a higher portion of total DOPAC was reported as conjugate in an area referred to as frontal cortex by Elchisak et al (1977) (550/0 vs. 38~ a discrepancy which may be due to the size of the brain sample used (627.5 ___24 mg vs. 28 +1.6 mg for prefrontal cortex in our study). On the other hand, at variance with our data and previous reports (Gordon et al, 1976;Elchisak et al, 1977;Bacwoulos et al, 1979;Dedek et al, 1979), Sarna et al (1984) using HPLC determination after organic solvent extraction found only 12~ of DOPAC as conjugate in striatum.…”

Section: Brain Conjugates At Basal Statecontrasting

confidence: 84%

“…Based on probenecid experiments, conjugated DOPAC and HVA were shown to be cleared from brain faster than the free acids (Gordon et al, 1976;Swahn and Wiesel, 1976;Elchisak et aL, 1977;Bacopoulos et al, 1979;Dedek et al, 1979;Sarna et al, 1984).…”

Section: Introductionmentioning

confidence: 98%

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Free and conjugated 3, 4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation

Tavitian

Peyrin

Dalmaz

et al. 1986

J. Neural Transmission

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We have determined free and conjugated 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in discrete brain areas of rats. Conjugated HVA or DOPAC accounted for 22-38% of total acids in striatum, mesolimbic tissue or prefrontal cortex. Activation of dopamine (DA) metabolism by a single injection of pipotiazine palmitic ester (PPZ), a long-lasting neuroleptic, increased free acid levels (DOPAC and HVA) at either dose and conjugate levels after 32 or 50 mg/kg. 48 hours after PPZ-32 mg/kg, the observed increases of conjugates could exceed in some cases those of corresponding free acids. About half of total DOPAC and HVA were conjugated in hypothalamus, PPZ moderately increased free DOPAC (at 32 mg/kg) but did not elevate significantly the conjugated form. It is concluded that sulfation is an important pathway for DOPAC and HVA metabolism in brain and that the determination of both free and conjugated DOPAC or/and HVA may shed additional lights on regional DA metabolism and the effect of drugs thereon.

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Section: Brain Conjugates At Basal Statesupporting

confidence: 95%

Section: Brain Conjugates At Basal Statecontrasting

confidence: 84%

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Free and conjugated 3, 4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation

Tavitian

Peyrin

Dalmaz

et al. 1986

J. Neural Transmission

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“…• OM 0.07 Tim. (min) FHV A leave the brain as free acids or sulfate con jugates via probenecid-sensitive transport directly into the circulation (Neff et al, 1967;Gordon et al , 1976;Grabowska-Anden et aI., 1984) or into the cerebrospinal fluid. We believe that the local trans port into the circulation plays a major role in human brain.…”

Section: Fdopa Modelmentioning

confidence: 99%

Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[¹⁸F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

Kuwabara

Cumming

Reith

et al. 1993

J Cereb Blood Flow Metab

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Summary: DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters do pamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboHlation coefficient (�) of 6-esp]fluoro-DOPA (PDOPA) to denote the relative ac tivity of L-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer me tabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of � in the presence of the inherent error of PET. To improve the accuracy of the kf estimates by optimizing the number of parameters, we introduced bi ological constraints which included a tracer partition vol-

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“…In this regard, the efflux activity of neurotransmitter metabo-lites from the cerebrospinal fluid to the blood may be an important physiological function. In this regard, it was suggested that some neurotransmitter metabolites are transported via the organic anion transport system; 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) are actively transported from the cerebrospinal fluid into the blood by an energy-dependent, probenecid-sensitive transporter (7).…”

Section: Introductionmentioning

confidence: 99%

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

et al. 2003

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Abstract. The purpose of the present study was to elucidate the expression of human organic anion transporter 1 (hOAT1) and hOAT3 in the choroid plexus of the human brain and their interactions with neurotransmitter metabolites using stable cell lines. Immunohistochemical analysis revealed that hOAT1 and hOAT3 are expressed in the cytoplasmic membrane and cytoplasm of human choroid plexus. Neurotransmitter metabolites, namely, 5-methoxyindole-3-acetic acid (5-MI-3-AA), homovanillic acid (HVA), vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HI-3-AA), N-acetyl-5-hydroxytryptamine (NA-5-HTT), melatonin, 5-methoxytryptamine (5-MTT), 3,4-dihidroxymandelic acid (DHMA), 5-hydroxytryptophol, and 5-methoxytryptophol (5-MTP), but not methanephrine (MN), normethanephrine (NMN), and 3-methyltyramine (3-MT), at 2 mM, inhibited para-aminohippuric acid uptake mediated by hOAT1. On the other hand, melatonin, 5-MI-3-AA, NA-5-HTT, 5-MTT, 5-MTP, HVA, 5-HI-3-AA, VMA, DOPAC, 5-hydroxytryptophol, and MN, but not 3-MT, DHMA, and NMN, at 2 mM, inhibited estrone sulfate uptake mediated by hOAT3. Differences in the IC 50 values between hOAT1 and hOAT3 were observed for DHMA, DOPAC, HVA, 5-HI-3-AA, melatonin, 5-MI-3-AA, 5-MTP, 5-MTT, and VMA. HOAT1 and hOAT3 mediated the transport of VMA but not HVA and melatonin. These results suggest that hOAT1 and hOAT3 are involved in the efflux of various neurotransmitter metabolites from the cerebrospinal fluid to the blood across the choroid plexus.

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

Cited by 62 publications

References 12 publications

Free and conjugated 3, 4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation

Free and conjugated 3, 4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation

Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[¹⁸F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

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

Cited by 62 publications

References 12 publications

Free and conjugated 3, 4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation

Free and conjugated 3, 4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation

Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[18F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

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Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[¹⁸F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects