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Fusaric acid-induced elevation of homovanillic acid in the CSF as an index of brain noradrenaline synthesis.

The effect of the dopamine-beta-hydroxylase inhibitor, fusaric acid (FA), on cerebrospinal fluid (CSF) homovanillic acid (HVA) was studied in pentobarbitone-anesthetized rats. Idazoxan, a selective alpha 2-antagonist, accentuated the FA-induced HVA elevation in CSF while alpha-methyldopa pretreatment prevented this effect of FA on the HVA level in CSF. These results could indicate that the rate of dopamine synthesis in noradrenaline neurons could be the main determinant of the FA-induced HVA elevation.

Animals↗

Monoamine oxidase (MAO), 5-hydroxyindole acetic acid (5 HIAA) and homovanillic acid (HVA) in motor neuron disease.

Thrombocyte monoamine oxidase (MAO) activity and concentrations of 5-hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) in the cerebrospinal fluid (CSF) were studied in patients with motor neuron disease (MND) and healthy controls. The MAO activity in MND (n = 32) did not differ from age and sex-matched controls (n = 27) or from healthy relatives (n = 9) and no difference was found between advanced and mild cases. In an attempt to explain divergent results from other studies, the effect of storage time on analysis of platelet concentration was studied in three healthy subjects and in three patients with MND. No difference was observed between the groups. No differences were found between the MND group (n = 28) and healthy controls (n = 18) with regard to CSF levels of 5-HIAA and HVA, except for an increase of 5-HIAA among males with MND. The results of this study do not confirm earlier studies that have reported extensive changes in the variables analyzed in patients with MND.

Blood Platelets↗

Analysis of cat retina for dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid.

Twenty retinas from 10 cats were evaluated for dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA) by high pressure liquid chromatography and electrochemical detection. Dopamine was present in all 20 retinas at a mean concentration of 3.00 +/- 0.54 ng/mg protein. Dihydroxyphenylacetic acid, 3-MT and HVA were detected in 16, 14 and 9 retinas respectively. In retinas in which these metabolites were detectable, they were present in the following mean concentrations: DOPAC, 1.07 +/- 0.21 ng/mg protein; 3-MT, 3.44 +/- 0.97 ng/mg protein and HVA, 4.54 +/- 1.05 ng/mg protein. Significantly higher concentrations of 3-MT (p = 0.0108, paired t test) and HVA (p = 0.0166, paired t test) than DOPAC were present in cat retina. Linear correlation analysis between DA and its metabolites indicated that the 3-MT and DOPAC concentrations correlated well with each other and with the amount of DA in cat retina. The concentrations of the end product metabolite, HVA, had poor correlations with the concentrations of 3-MT, DOPAC or DA. These data indicated that once DA is released in cat retina it can be metabolized to 3-MT, DOPAC and HVA.

3,4-Dihydroxyphenylacetic Acid↗

Effect of ECT and imipramine treatment on the concentration of 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in the cerebrospinal fluid of depressed patients.

The influence of probenecid administration on 5HIAA and HVA concentrations in the CSF of depressed patients, was studied before and after treatment with imipramine or ECT. The average increase of the two metabolites in the CSF after probenecid was similar in the untreated depressed patients and in the same patients improved after both imipramine or ECT treatment. The treatment determined a significant increase in the CSF concentration of the acid metabolites also before the probenecid administration.

Adult↗

2-Guanidinoethanol increased dopamine release and 3,4-dihydroxyphenylacetic acid content, but not homovanillic acid content in the rat brain: electroneurochemical and enzymological studies.

The effects of 2-guanidinoethanol (GEt) on the release of monoamines and on the activity of their degrading enzymes were studied in order to investigate why 3,4-dihydroxyphenylacetic acid (DO-PAC) increased to a much greater extent than homovanillic acid (HVA) after GEt injection into rat brain. In differential pulse voltammograms recorded using an electrochemically treated carbon fiber electrode, two distinct oxidation peaks, one at 130mV (DOPAC peak) and the other at 300 mV (5-hydroxyindoleacetic acid (5-HIAA) peak), were observed. In the hippocampus, the DOPAC peak increased markedly compared to the peak height recorded prior to the intracerebroventricular injection of GEt (6 mumol). Although the DOPAC peak height increased to 350% 4 hours after GEt injection, the 5-HIAA peak showed no change. In the striatum, the DOPAC peak increased to 150% 3 hours after GEt injection. Serial changes in the extracellular levels of DOPAC, HVA, and 5-HIAA were monitored in the striatum after GEt injection, using an in vivo brain micro-dialysis technique. Although the DOPAC levels strated to increase 80 minutes after GEt injection, HVA and 5-HIAA levels showed no change. On the other hand, monoamineoxidase, which metabolizes dopamine to DOPAC, was not activated and catechol-O-methyltransferase, which metabolizes DOPAC to HVA, were not inhibited by 5 mM of GEt in vitro. These data suggested that GEt increased the release of dopamine, but not of serotonin, and that GEt might restrict the DOPAC transport system.

3,4-Dihydroxyphenylacetic Acid↗

Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson's disease.

High-performance liquid chromatography with electrochemical detection has been employed to analyze ultrafiltrates of cerebrospinal fluid of Parkinson's Disease (PD) patients and age-matched controls for the dopamine (DA) metabolites homovanillic acid (HVA) and 5-S-cysteinyldopamine (5-S-CyS-DA). The mean level of HVA in the CSF of PD patients, measured 5 days after withdrawal from L-DOPA therapy, was significantly lower than that measured in controls. By contrast, mean levels of 5-S-CyS-DA were not significantly different in the CSF of PD patients taking L-DOPA (PD-LT patients) the same patients 5 days after discontinuing this drug (PD-LW patients) or controls. However, the mean 5-S-CyS-DA/HVA concentration ratio was significantly (p < 0.05) higher in the CSF of PD-LW patients compared to controls. Although the PD patient population employed in this study had been diagnosed with the disease several years previously and had been treated with L-DOPA for prolonged periods of time the results of this study suggest that low CSF levels of HVA and a high 5-S-CyS-DA/HVA ratio together might represent useful markers for early diagnosis of PD. The high 5-S-CyS-DA/HVA ratio observed in the CSF of PD-LW patients also provides support for the hypothesis that the translocation of glutathione or L-cysteine into neuromelanin-pigmented dopaminergic cell bodies in the substantia nigra might represent an early event in the pathogenesis of PD.

Aged↗

Determination of vanillylmandelic, 5-hydroxyindoleacetic and homovanillic acid in urine by isocratic liquid chromatography.

A new isocratic HPLC method, employing electrochemical detection, is described for the determination of urinary vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid. The main advantages of this technique are: simplicity, simultaneous determination of all analytes, the absence of an extraction procedure, isocratic elution and low cost. The diluted urine is injected onto a C18 reversed phase column. The mobile phase is potassium dihydrogenphosphate buffer containing 1-heptanesulphonic acid, methanol and acetonitrile. The calibration curves are linear from 0.1 to 50 mg/l; the precision data show CV less than 2.36% for within-day assay and less than 2.72% for day-to-day assays. The mean recoveries for supplemented samples are 98.2 to 102.0% for vanillylmandelic acid, 99.6 to 103.9% for 5-hydroxyindoleacetic acid and 98.7 to 102.0% for homovanillic acid. In comparisons of the present method with Radjaipur's extraction method (Radjaipur M. et al., Eur J Clin Chem Clin Biochem 1994; 32:609-13) the slopes for the three analytes were nearly 1, and the confidence region of the intercepts was close to 0. In conclusion the technique seems to be suitable for routine determination of the three analytes, especially for mass screening purposes.

Adult↗

Urinary 4-hydroxy-3-methoxymandelic (vanillylmandelic) acid, 4-hydroxy-3-methoxyphenylacetic (homovanillic) acid, and 5-hydroxy-3-indoleacetic acid determined by liquid chromatography with electrochemical detection.

We describe a simple liquid-chromatographic assay of urinary 4-hydroxy-3-methoxymandelic (vanillylmandelic) acid, 4-hydroxy-3-methoxyphenylacetic (homovanillic) acid, and 5-hydroxy-3-indoleacetic acid with electrochemical detection, with direct injection of the sample. The first two analytes are measured simultaneously; 5-hydroxy-3-indoleacetic acid is measured separately. Chromatographic conditions for assay of the three were: column temperature, 65 and 60 degrees C; mobile phase, potassium phosphate buffer (0.2 mol/L, pH 3.0) for 6 min, then potassium phosphate buffer plus acetonitrile (9/1 by vol) for 20 min; flow rate, 0.7 mL/min; oxidation potential, 600 and 450 mV vs an Ag/AgCl reference electrode; and sensitivity, 40 and 160 nA at full scale. Values so obtained agreed well with those obtained for samples that were first solvent-extracted.

Chromatography, High Pressure Liquid↗