Disease relevance of Homoprotocatechuic acid

• The monolateral microinjection of the [d-Ala2]] analog (3 to 6 micrograms) into the caudate nucleus increased the concentration of dihydroxyphenylacetic acid in the injected side, whereas bilateral injection increased the concentration of this compound in both caudate nuclei and caused catalepsy [1].
• We determined whether patterns of plasma levels of dopa, norepinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid would distinguish patients with orthostatic hypotension associated with multiple system atrophy, pure autonomic failure, or deficiency of dopamine-beta-hydroxylase [2].
• Here we show that stable transfection of parkin in the human dopaminergic neuroblastoma cell line SH-SY5Y markedly reduced the activities of both monoamine oxidase (MAO) A and B. The amount of 3,4-dihydroxyphenylacetic acid, which is produced during dopamine oxidation by MAO, was greatly reduced by parkin overexpression [3].
• Based on the levels of ACE activity, DOPAC, and HVA per milliliter of CSF, two discriminant functions were derived and resulted in the correct classification of 71% of all subjects (n = 38) into Alzheimer's disease, Parkinson's disease, and neurologically healthy control groups [4].
• In contrast, DEA/NO failed to promote toxicity by DOPAC and HGA, probably due to their ability to undergo oxidative polymerization, leading to the formation of melanins [5].

Psychiatry related information on Homoprotocatechuic acid

• Feeding induced by food deprivation is accompanied by an increased production of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the brains of rats [6].
• RESULTS: We report here that Nur77-deficient mice display enhanced spontaneous locomotor activity, greater sensitivity to a small dose of the dopamine D(2) receptor agonist quinpirole acting mainly at autoreceptor sites, and higher levels of the dopamine metabolite DOPAC relative to wild-type mice [7].
• From dose- and time-response studies, it appeared that 30 mg/kg i.p. of GM1 administered daily for approximately 23 days resulted in an approximately 80% restoration of the DA level and complete restoration of the 3,4-dihydroxyphenylacetic acid (DOPAC) content [8].
• Dopamine and DOPAC concentrations in the paraventricular dialysate increased 140% and 19%, respectively, above baseline values during exposure to the receptive female and 280% and 31%, respectively, during copulation [9].
• Stereotyped behavior was measured during the hour after administration of apomorphine; levels of the dopamine metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum were assessed at the end of this period (2 hr after administration of haloperidol) [10].

High impact information on Homoprotocatechuic acid

• It has been suggested that expression of TH is regulated trans-synaptically because on deafferentation of the bulb there is a marked decrease in the contents of TH, dopamine and 3,4-dihydroxyphenylacetic acid, which, however, return to normal levels after regeneration of the primary afferents [11].
• Moreover, pharmacological investigations suggest that the catecholamine peak measured in vivo in the rat neostriatum should be attributed to 3, 4-dihydroxyphenylacetic acid (DOPAC), suggesting that our technique may be a useful means of following dopaminergic activity in vivo [12].
• Twenty-four hours after unilateral injection of cholera enterotoxin into the rat substantia nigra there is an increase, in the striatum on the injected side, of basal adenylate cyclase activity, 3,4-dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylacetic acid [13].
• The restored tyrosinase enzymatic activity was detected by dihydroxyphenylacetic acid (DOPA) staining of hair follicles in the treated skin [14].
• Plasma, cerebrospinal fluid (CSF), and urine samples were obtained before and during debrisoquin administration and were assayed for their content of norepinephrine and dopamine metabolites, ie, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and dihydroxyphenylacetic acid [15].

Chemical compound and disease context of Homoprotocatechuic acid

• In the first hour after hypoxia, DOPAC and HVA levels rose quickly, whereas 5-HIAA levels remained suppressed [16].
• We tested patients with PD, patients with Alzheimer's type of senile dementia, and a control group neuropsychologically, and we determined their CSF levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindolacetic acid, serotonin, and acetylcholinesterase [17].
• During ischemia, extracellular dopamine increased dramatically (156 times baseline), as did 3-methoxytyramine (3-MT), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (15-25% of baseline) [18].
• Hydrogen peroxide as a mediator of dopac-induced effects on melanoma cells [19].
• Analysis of the degradation products of melanin from dopac-treated melanoma cells after hydriodic acid (HI) hydrolysis revealed the presence of aminohydroxy-phenylacetic acid (AHPAc) [19].

Biological context of Homoprotocatechuic acid

• Tyrosinase gene correction was also confirmed by restriction fragment length polymorphism analysis and DNA sequencing from skin that was positive for DOPA staining and melanin synthesis [14].
• Dihydroxyphenylacetic acid (DOPAC) levels and vesicular storage capacity matured faster in mesencephalic than in diencephalic cultures, but no sex differences were observed [20].
• Furthermore, differences in dihydroxyphenylacetic acid levels, which were about twice as high on the contralateral side yet still reduced with respect to untreated mice, supported our assumption that the molar TH activity was increased on the untreated side, possibly due to an intrinsic compensatory up-regulation [21].
• Release of NPY and catecholamines was linear with time; SCG neurons exhibited a basal NPY secretory rate of approximately 0.9-3 fmol NPY immunoreactivity/10(4) cells/hr, and basal DOPAC plus HVA accumulation was about 10-20 pmol total metabolites/10(4) cells/hr [22].
• The circadian rhythm of DOPAC could be reproducibly demonstrated over at least 4 successive days in individual subjects [23].

Anatomical context of Homoprotocatechuic acid

• The conditioned circling paradigm was employed in an attempt to replicate reports that levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were increased in the striatum and nucleus accumbens septi (NAS) contralateral to the direction of circling [24].
• In hippocampus, the extracellular concentration of DOPAC may reflect NE biosynthesis, and thus the enhanced DOPAC response in the chronically stressed rats suggests an increase in NE synthesis [25].
• BD rats have high levels of viral nucleic acid in the prefrontal cortex (PFC), abnormal mesocortical dopamine activity (elevated levels of DOPAC in PFC), yet no alteration in specific binding of D1 or D2 receptor radioligands in PFC [26].
• Since the plasma DOPAC concentration appears to reflect central nervous system dopaminergic neuronal activity, the present demonstration of a circadian rhythm of plasma DOPAC suggests that the activity of central nervous system DA-containing cells is higher during the day than at night [23].
• The afternoon decrease of TIDA neuronal activity, as determined by 3,4-dihydroxyphenylacetic acid concentration in the median eminence, was also advanced from 1400 to 1300 h [27].

Associations of Homoprotocatechuic acid with other chemical compounds

• Ondansetron (0.1 and 1 mg/kg) and (S)-zacopride (0.1 mg/kg), two 5-HT3 antagonists, significantly impaired the increase of accumbal DA release induced by 20 Hz DRN stimulation but did not affect either the decrease of striatal DA release or the increase in DOPAC outflow in both structures [28].
• At the distal end of the dialysis tube, the Ringer is collected every 10 to 20 min and directly injected into a high performance liquid chromatographer (HPLC) equipped with reverse phase octadecyl sulfate columns which separate DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) [29].
• Seven weeks following reversible chemical lesions produced by Triton X-100, DA and DOPAC levels and tissue weight as well as TH staining in the juxtaglomerular neurons returned to control levels [30].
• In vivo microdialysis was used to obtain samples for measurements of norepinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid in conscious animals before and after yohimbine injection (1 mg/kg IV) beginning 24 hours after probe implantation [31].
• Neurofilaments were incubated in the presence of oxidized L-dopa, dopamine, or dopac and then analyzed by SDS-PAGE and protein staining or immunoblotting with monoclonal antibodies specific for neurofilament subunit proteins [32].

Gene context of Homoprotocatechuic acid

• In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC [33].
• Pretreatment with the receptor antagonists PTH(7-34) or PTHrP(7-34) completely blocked the subsequent DOPAC response to ICV PTH or PTHrP, respectively [34].
• These results suggest that virally delivered GDNF promotes the recovery of nigral dopaminergic tone (i.e.: increased DA and DOPAC levels) and improves behavioral performance (i.e.: decreased rotations, increased locomotion) in rodents with extensive nigrostriatal dopaminergic denervation [35].
• Furthermore, electrochemical analysis revealed a more than 70% decrease in the levels of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the striatum of the WT control COX-1(-/-) and COX-2(-/-) mutant mice [36].
• There was a significant increase in the area under the curve (AUC) of DOPAC during COMT-inhibition compared to the baseline profile (p = 0.009) [37].

Analytical, diagnostic and therapeutic context of Homoprotocatechuic acid

• Using in vivo microdialysis, it was determined that the basal extracellular concentrations of NE and 3,4-dihydroxyphenylacetic acid (DOPAC) in hippocampus were the same in the two groups [25].
• Addition of 50 mM KCl to the SNR perfusion solution produced a 3.5-fold increase in DA and a 50% reduction in dihydroxyphenylacetic acid (DOPAC) in the SNR; in contrast, this manipulation in the SNR caused DA release in the striatum to be decreased by 20%, while striatal DOPAC was increased by 50% [38].
• In parallel experiments using ex vivo changes in the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC) to dopamine as an index of changes in dopamine turnover, a similar early depression and delayed increase of dopamine turnover in nucleus accumbens, with no change in striatum, was found after an intraperitoneal injection of FG 7142 [39].
• 3,4-Dihydroxyphenylacetic acid, also assayed by high pressure liquid chromatography, was undetectable in both normal pituitary tissue and prolactinomas [40].
• By 1 min of immobilization, plasma NE and EPI levels had already reached peak values, and plasma levels of DOPA, DHPG, DOPAC, and MHPG were increased significantly from baseline, whereas plasma DA and HVA levels were unchanged [41].

References