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1.
Clin Exp Hypertens ; 42(2): 118-125, 2020.
Article in English | MEDLINE | ID: mdl-30821508

ABSTRACT

Background and Objective: Evaluate the activity of dopamine-ß-hydroxylase (DßH) as well as the effect of the DßH inhibitor nepicastat upon enzyme activity and levels of dopamine (DA) and norepinephrine (NE) in the rat left ventricle, kidney, and adrenal glands.Methods: DßH assay consisted of the enzymatic hydroxylation of tyramine into octopamine, and DA and NE tissues levels were quantified by HPLC-ED.Results: Nepicastat (30 mg/kg, p.o.) reduced DßH activity by 93% and 80% in the adrenals at 4 h and 8 h postdrug administration, accompanied by significant reductions in NE and epinephrine tissue levels and an increase in DA levels and of DA/NE tissue ratios, with similar findings for NE, DA and of DA/NE tissue ratios in left ventricle and kidney. DßH activity in the left ventricle and kidney showed a high degree of variability, which does not allow corroboration of the effects of nepicastat upon catecholamine tissue levels.Conclusion: The assay of DßH activity in heart and kidney lacks the necessary robustness, but DßH activity in the adrenals appears to be an appropriate marker. However, the effect size upon DA/NE tissue ratios (an indirect measure of DßH activity) as induced by nepicastat was very similar in sympathetically innervated tissues, left ventricle and kidney, and the adrenal medulla.


Subject(s)
Dopamine beta-Hydroxylase/drug effects , Enzyme Inhibitors/pharmacology , Imidazoles/pharmacology , Norepinephrine/metabolism , Thiones/pharmacology , Adrenal Glands/physiology , Animals , Dopamine/metabolism , Dopamine beta-Hydroxylase/pharmacology , Heart Ventricles/drug effects , Hypertension/physiopathology , Kidney/physiology , Male , Rats , Rats, Wistar
2.
J Diabetes Res ; 2016: 3793781, 2016.
Article in English | MEDLINE | ID: mdl-27366756

ABSTRACT

High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent ß-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated ß-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 ß-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 ß-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 ß-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 ß-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.


Subject(s)
Insulin-Secreting Cells/drug effects , Islets of Langerhans/metabolism , Transcriptome/genetics , Acetylserotonin O-Methyltransferase/drug effects , Acetylserotonin O-Methyltransferase/genetics , Animals , Arylalkylamine N-Acetyltransferase/drug effects , Arylalkylamine N-Acetyltransferase/genetics , Catechol O-Methyltransferase/drug effects , Catechol O-Methyltransferase/genetics , Cell Line , Dopa Decarboxylase/drug effects , Dopa Decarboxylase/genetics , Dopamine Plasma Membrane Transport Proteins/drug effects , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine beta-Hydroxylase/drug effects , Dopamine beta-Hydroxylase/genetics , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/metabolism , Mice , Monoamine Oxidase/drug effects , Monoamine Oxidase/genetics , Oleic Acid/pharmacology , Palmitic Acid/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/drug effects , Serotonin Plasma Membrane Transport Proteins/genetics , Transcriptome/drug effects , Tryptophan Hydroxylase/drug effects , Tryptophan Hydroxylase/genetics , Tyrosine 3-Monooxygenase/drug effects , Tyrosine 3-Monooxygenase/genetics
3.
Mov Disord ; 29(14): 1710-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25297066

ABSTRACT

The dramatic response of most motor and some nonmotor symptoms to dopaminergic therapies has contributed to maintaining the long-established identity of Parkinson's disease (PD) as primarily a nigrostriatal dopamine (DA) deficiency syndrome. However, DA neurotransmission may be neither the first nor the major neurotransmitter casualty in the neurodegenerative sequence of PD. Growing evidence supports earlier norepinephrine (NE) deficiency resulting from selective degeneration of neurons of the locus coeruleus and sympathetic ganglia. Dopaminergic replacement therapy therefore would seem to neglect some of the motor, behavioral, cognitive, and autonomic impairments that are directly or indirectly associated with the marked deficiency of NE in the brain and elsewhere. Therapeutic strategies to enhance NE neurotransmission have undergone only limited pharmacological testing. Currently, these approaches include selective NE reuptake inhibition, presynaptic α2 -adrenergic receptor blockade, and an NE prodrug, the artificial amino acid L-threo-3,4-dihydroxyphenylserine. In addition to reducing the consequences of deficient noradrenergic signaling, enhancement strate gies have the potential for augmenting the effects of dopaminergic therapies in PD. Furthermore, early recognition of the various clinical manifestations associated with NE deficiency, which may precede development of motor symptoms, could provide a window of opportunity for neuroprotective interventions.


Subject(s)
Dopamine beta-Hydroxylase/deficiency , Locus Coeruleus/drug effects , Motor Activity/drug effects , Norepinephrine/deficiency , Norepinephrine/pharmacology , Parkinson Disease/drug therapy , Animals , Autonomic Nervous System Diseases/metabolism , Dopamine/metabolism , Dopamine beta-Hydroxylase/drug effects , Dopamine beta-Hydroxylase/metabolism , Humans , Locus Coeruleus/metabolism , Norepinephrine/metabolism , Parkinson Disease/genetics
4.
Neuroscience ; 241: 52-8, 2013 Jun 25.
Article in English | MEDLINE | ID: mdl-23518225

ABSTRACT

Little is known about the influence of arsenic (As) exposure on monoamine neurotransmitters and the underlying mechanisms, although arsenic toxicity on the central nervous system has been well documented. In the present study, the levels of norepinephrine (NE), dopamine (DA), and 5-HT were determined by high performance liquid chromatography in the cerebrum and cerebellum of mice exposed to 1, 2 and 4 ppm As2O3 through drinking water for 60 days. The ultra-structural change of vesicles in the synapses of mice brains was observed by transmission electron microscopy; the mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) as NE, DA and 5-HT synthetases were quantitatively assessed by real time reverse transcription-polymerase chain reaction. It was shown that the concentrations of NE, DA and 5-HT in the cerebrum or cerebellum of mice exposed to As were significantly lower than those in the control group. The number of synaptic vesicles significantly decreased in the brain of mice exposed to As. Moreover, the expressions of TH, TPH and DBH genes were significantly lower in the brains of mice exposed to As than those in the controls. These results suggested that subchronic exposure to As might decrease the concentrations of the three monoamine neurotransmitters in the mouse brain and downregulate TH, TPH and DBH gene expressions. It was also indicated that the decreased concentrations of the three monoamine neurotransmitters in the brain might be related to the down-regulated gene expressions of these synthetases by As.


Subject(s)
Arsenic/toxicity , Brain/drug effects , Brain/metabolism , Ligases/drug effects , Neurotransmitter Agents/metabolism , Animals , Biogenic Amines/biosynthesis , Chromatography, High Pressure Liquid , Dopamine beta-Hydroxylase/biosynthesis , Dopamine beta-Hydroxylase/drug effects , Ligases/biosynthesis , Mice , Microscopy, Electron, Transmission , RNA, Messenger , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Synapses/ultrastructure , Tryptophan Hydroxylase/biosynthesis , Tryptophan Hydroxylase/drug effects , Tyrosine 3-Monooxygenase/biosynthesis , Tyrosine 3-Monooxygenase/drug effects
5.
Hypertension ; 52(2): 351-8, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18606900

ABSTRACT

The link among blood pressure, sympathetic output, and brain neurons producing catecholamines is well documented. Nevertheless, their intrinsic properties and any alterations in signaling characteristics between normotensive and hypertensive phenotypes remain unknown. Here, we directly compared neurophysiological properties of catecholamine release of C1 and A2 neurons of the spontaneously hypertensive rat and Wistar rat in organotypic slices. C1 and A2 areas were studied because both are widely implicated in the pathophysiology of hypertension. Catecholaminergic neurons were visualized using viral vectors to express green fluorescent protein. Microamperometry revealed that C1 axonal varicosities of spontaneously hypertensive but not normotensive Wistar rats release a transmitter predominantly (approximately 86%) in very large quanta, comparable in catecholamine load to adrenal chromaffin granules. Because quantal size affects the spread of transmitter in the extracellular space, this may enhance the impact of C1 varicosities on their downstream targets and increase sympathetic drive in the hypertensive rat. Electrophysiological properties and Ca2+ handling were studied using patch clamp and confocal imaging. Although overall electrophysiological characteristics of C1 and A2 neurons were comparable between strains, the characteristic angiotensin-II-induced Ca2+ mobilization was reduced in A2 neurons of the spontaneously hypertensive rat. Because A2 neurons are a part of a homeostatic antihypertensive circuit, this could reduce their restraining influence on blood pressure. Thus, we have revealed an increased quantal size in C1 varicosities and a reduced responsiveness of A2 neurons of the spontaneously hypertensive rat to angiotensin II. Both effects could contribute to elevated sympathetic activity and blood pressure in the spontaneously hypertensive rat.


Subject(s)
Brain Stem/drug effects , Catecholamines/metabolism , Hypertension/physiopathology , Neurons/metabolism , Angiotensin II/pharmacology , Animals , Brain Stem/metabolism , Catecholamines/analysis , Disease Models, Animal , Dopamine beta-Hydroxylase/drug effects , Dopamine beta-Hydroxylase/metabolism , Electrophysiology , Hypertension/metabolism , Losartan/pharmacology , Neurons/drug effects , Norepinephrine/metabolism , Phenethylamines/metabolism , Probability , Random Allocation , Rats , Rats, Inbred SHR , Rats, Wistar , Reference Values , Sensitivity and Specificity
6.
Toxicol Appl Pharmacol ; 221(3): 261-7, 2007 Jun 15.
Article in English | MEDLINE | ID: mdl-17498763

ABSTRACT

Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a beta(1)- and beta(2)-selective antagonist, respectively, suggesting the role of beta-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DbetaH) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferation and adrenaline production. Expression of alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an alpha7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and DbetaH expression as well as adrenaline production. Taken together, through the action on alpha7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and beta-adrenergic activation. These data reveal the contributory role alpha7-nAChR and beta-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer.


Subject(s)
Adenocarcinoma/metabolism , Alkaloids/pharmacology , Cell Proliferation/drug effects , Colonic Neoplasms/metabolism , Epinephrine/metabolism , Nicotine/pharmacology , Receptors, Nicotinic/drug effects , Alkaloids/metabolism , Dopamine beta-Hydroxylase/drug effects , Dopamine beta-Hydroxylase/metabolism , Dose-Response Relationship, Drug , Humans , Nicotine/metabolism , Nicotinic Agonists/metabolism , Nicotinic Agonists/pharmacology , Phenylethanolamine N-Methyltransferase/drug effects , Phenylethanolamine N-Methyltransferase/metabolism , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/physiology , Receptors, Nicotinic/metabolism , Signal Transduction/drug effects , Tumor Cells, Cultured , Tyrosine 3-Monooxygenase/drug effects , Tyrosine 3-Monooxygenase/metabolism , Up-Regulation , alpha7 Nicotinic Acetylcholine Receptor
7.
Acta Histochem ; 107(1): 11-22, 2005.
Article in English | MEDLINE | ID: mdl-15866282

ABSTRACT

The aim of the present study was the demonstration of mechanisms of regulation of activity of chromaffin cells in the adrenal gland of Rana ridibunda (Anura-Amphibia). Previous studies have shown that endothelin-1 is an important factor for the maintenance of adrenal gland function. On the basis of these findings, frogs were injected with [Ala(1,3,11,15)]-endothelin-1 (0.025 mg/0.2 ml), which is a selective agonist of the endothelin B receptor, whereas control animals were injected with Ringer solution (0.2 ml). The adrenal glands were removed at 5, 20, and 60 min after injection and fixed, embedded in paraffin wax and stained by histological and immunohistochemical means, applied on adjacent 4-microm-thick sections. Sections were stained with hematoxylin and eosin for overall tissue analysis and, in parallel, serotonin was localized using the streptavidin-biotin complex technique while dopamine beta-hydroxylase and serotonin 2A receptors were shown by the peroxidase-antiperoxidase (PAP)-3,3'-diaminobenzidine tetrachloride (DAB) method. After injection of [Ala(1,3,11,15)]-endothelin-1, chromaffin cells secreted serotonin and synthesized dopamine beta-hydroxylase. In conclusion, these findings suggest that [Ala(1,3,11,15)]-endothelin-1 stimulates chromaffin cell activity in frog adrenal glands. Moreover, the presence of serotonin 2A receptors in chromaffin cells indicates that these cells are also targets for serotonin and that there is an autocrine signaling pathway in chromaffin cells. This is the first report providing data on the effects of endothelin-1 on chromaffin cells in frog adrenal glands.


Subject(s)
Adrenal Glands/cytology , Adrenal Glands/drug effects , Autocrine Communication/physiology , Chromaffin Cells/metabolism , Endothelin-1/pharmacology , Serotonin/metabolism , Adrenal Glands/ultrastructure , Animals , Chromaffin Cells/drug effects , Chromaffin Cells/ultrastructure , Dopamine beta-Hydroxylase/drug effects , Dopamine beta-Hydroxylase/ultrastructure , Immunohistochemistry , Ranidae , Receptor, Serotonin, 5-HT2A/drug effects , Receptor, Serotonin, 5-HT2A/ultrastructure , Serotonin/analysis , Staining and Labeling
9.
J Comp Neurol ; 427(4): 617-33, 2000 Nov 27.
Article in English | MEDLINE | ID: mdl-11056468

ABSTRACT

Previous studies have shown that gonadectomy in adult male rats induces a complex series of region- and time-specific changes in the density of presumed cerebral cortical dopamine axons that are immunoreactive for tyrosine hydroxylase. The present study asked whether noradrenergic cortical afferents also show hormone sensitivity by assaying axons immunoreactive for the enzyme dopamine-beta-hydroxylase in representative areas of acutely and chronically gonadectomized and sham-operated adult male rats. Catecholamine afferents (both tyrosine hydroxylase-immunoreactive and dopamine-beta-hydroxylase-immunoreactive) were also quantified in gonadectomized rats supplemented with testosterone propionate, with 17-beta-estradiol, or with 5-alpha-dihydrotestosterone. Analyses of noradrenergic (dopamine-beta-hydroxylase) afferents revealed no differences in axon appearance or density among the hormonally intact and hormonally manipulated groups. However, analyses of tyrosine hydroxylase immunoreactivity revealed an unexpected division of labor among ovarian and testicular hormones in ameliorating the effects of acute verses chronic hormone deprivation on these afferents. Estradiol replacement attenuated the decreases in immunoreactivity induced by acute gonadectomy, but was ineffective in suppressing changes in immunoreactivity stimulated by chronic gonadectomy. In contrast, supplementing gonadectomized animals with dihydrotestosterone provided no protection from acute decreases in innervation, but fully attenuated both the supragranular decreases and infragranular increases in tyrosine hydroxylase-immunoreactive axon density that mark the association cortices of chronically gonadectomized rats. Together these findings indicate both long- and short-term effects of gonadectomy on cortical catecholamines, principally target dopamine afferents, and that chronic gonadectomy, which selectively disturbs dopamine innervation in the prefrontal cortices, involves a compromise in androgen signaling pathways.


Subject(s)
Axons/chemistry , Cerebral Cortex/chemistry , Dopamine beta-Hydroxylase/analysis , Orchiectomy , Tyrosine 3-Monooxygenase/analysis , Afferent Pathways/chemistry , Animals , Axons/drug effects , Catecholamines/analysis , Cerebral Cortex/drug effects , Dihydrotestosterone/blood , Dihydrotestosterone/pharmacology , Dopamine beta-Hydroxylase/drug effects , Estradiol/blood , Estradiol/pharmacology , Gonadal Steroid Hormones/blood , Gonadal Steroid Hormones/pharmacology , Gonads/chemistry , Male , Orchiectomy/methods , Rats , Rats, Sprague-Dawley , Testosterone/blood , Testosterone/pharmacology , Tyrosine 3-Monooxygenase/drug effects
10.
Mech Dev ; 92(2): 169-77, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10727856

ABSTRACT

During differentiation of sympathetic neurons in chick embryos, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) mRNAs become detectable during the same developmental period and are both induced by BMP 4. Later during sympathetic ganglion development, DBH is detectable in TH-positive and -negative cells. Moreover, BMPs reduce DBH mRNA in cultures of sympathetic neurons while leaving TH unaffected. The data provide evidence for a common regulation of TH and DBH early during sympathetic neuron differentiation and indicate that BMPs promote their initial expression but not the maintenance during later development. The time course of Phox2a and 2b expression suggests an evolutionary conserved role in noradrenergic induction. In addition, Phox2a, Phox2b, and c-ret may be involved in the differentiation of cholinergic sympathetic neurons.


Subject(s)
Dopamine beta-Hydroxylase/genetics , Drosophila Proteins , Homeodomain Proteins/genetics , Nerve Tissue Proteins/genetics , Neurons/physiology , Sympathetic Nervous System/physiology , Transcription Factors/genetics , Transforming Growth Factor beta , Tyrosine 3-Monooxygenase/genetics , Animals , Bone Morphogenetic Protein 4 , Bone Morphogenetic Protein 7 , Bone Morphogenetic Proteins/metabolism , Bone Morphogenetic Proteins/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cells, Cultured , Chick Embryo , Dopamine beta-Hydroxylase/drug effects , Embryonic Induction/drug effects , Embryonic Induction/genetics , Gene Expression Regulation, Developmental/drug effects , Homeodomain Proteins/drug effects , Nerve Tissue Proteins/drug effects , Neural Crest/drug effects , Neurons/drug effects , Proto-Oncogene Proteins/drug effects , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-ret , Receptor Protein-Tyrosine Kinases/drug effects , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Adrenergic/metabolism , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/embryology , Transcription Factors/drug effects , Tyrosine 3-Monooxygenase/drug effects , Tyrosine 3-Monooxygenase/metabolism
11.
Neurotoxicology ; 17(3-4): 753-9, 1996.
Article in English | MEDLINE | ID: mdl-9086498

ABSTRACT

Monoamine oxidase B (MAO-B) activity in platelets, serum dopamine-beta-hydroxylase (DBH) activity, and serum prolactin (PRL) were measured during a cross-sectional investigation in workers occupationally exposed to styrene. The study group consisted of 53 workers (33 men and 20 women) employed for 9.3 years on average (range 1-22) in reinforced plastics plants. Sixty industrial workers with no known exposure to chemicals and comparable as to age, sex and confounding variables were recruited as controls. The activities of MAO-B in platelet-rich plasma and of DBH in serum from exposed and control subjects were measured within the same run, using methods based on the liquid-chromatographic determination of the reaction products. Serum PRL was determined by both EIA and RIA. Blood samples had been collected between 8:00 and 9:00 a.m. A lower DBH activity was found in exposed as compared to control workers (GM: 7.25 U/ml serum vs. 10.11 U/ml serum; p < 0.01), whereas MAO-B activity was significantly lower in a heavily exposed subgroup (10.1 vs. 13.8 U/10(7) platelets; p = 0.05), but not in the whole sample (p = 0.07). Serum PRL was higher both in male (GM: 8.90 ng/ml vs. 6.05 ng/ml; p < 0.01) and female (GM: 12.6 ng/ml vs. 9.33 ng/ml; p < 0.05) styrene-exposed workers as compared to their respective controls. Dose-response relationships were found for abnormally low DBH and abnormally high PRL values, with a threshold occurring at metabolite levels corresponding to 8h-TWA styrene concentrations in air around 25 ppm. In summary, this study shows that long-term exposure to relatively low levels of styrene can affect DBH activity and basal serum PRL. Owing to its sensitivity, PRL is a useful biomarker to show impairments of dopaminergic control on pituitary secretion. Since DBH is expression of catecholamine secretion, its decreased activity could represent an indirect index of altered turnover rate of the physiological substrate (i.e.dopamine) at the neuronal level. However, a direct interference by styrene metabolites on enzyme activity cannot be ruled out. Platelet MAO-B activity seems to be less sensitive to styrene exposure.


Subject(s)
Blood Platelets/drug effects , Dopamine beta-Hydroxylase/drug effects , Monoamine Oxidase/drug effects , Neurotoxins/toxicity , Styrenes/toxicity , Adult , Female , Humans , Male , Middle Aged , Occupational Exposure , Styrene
12.
Neurotoxicology ; 17(3-4): 769-75, 1996.
Article in English | MEDLINE | ID: mdl-9086500

ABSTRACT

In a pilot study, serum dopamine beta-hydroxylase (DBH), platelets monoamine oxidase type B (MAO B) activities and basal plasma prolactin (PRL) were measured, among 10 workers occupationally exposed to toluene and 10 control subjects, preceding and immediately following vacation. Six exposed subjects were employed in an adhesive tape making industry and 4 in a paint making industry. Their median basal levels of urinary hippuric acid were 0.44 mmole/mmole creatinine (cr) (range 0.23-1.97) and 0.18 mmole/mmole cr (range 0.15-0.19) respectively, the second to last morning of the work week, preceding vacation. The level of basal urinary hippuric acid among the control group was 0.26 mmole/mmole cr (range 0.03-0.38). The workers from the adhesive tape plant reported a significantly higher number of symptoms experienced frequently (Kruskal, Wallis, p < 0.05). On a group basis, serum DBH was lowest among the workers from the adhesive tape plant, who had the highest levels of basal urinary hippuric acid. In addition, a negative relation was observed between hippuric acid and serum DBH, preceding and following vacation (Rho = -0.46, p = 0.05; Rho = -0.51, p = 0.03). The observed changes in serum DBH activity are consistent with its decrease in human, following long-term exposure to styrene, another aromatic hydrocarbon. The findings of this pilot study, on a limited number of individuals suggest that DBH may be a sensitive peripheral bioindicator. Further studies of larger groups should be done to confirm the decrease in serum DBH activity with toluene exposure and explore whether this alteration is related to the neurotoxic impairments associated with exposure.


Subject(s)
Dopamine beta-Hydroxylase/drug effects , Monoamine Oxidase/drug effects , Occupational Exposure , Toluene/toxicity , Adult , Female , Humans , Male , Middle Aged
13.
Biomed Environ Sci ; 8(2): 114-21, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7546340

ABSTRACT

Serum dopamine-beta-hydroxylase (DBH) inhibition has been reported in lead workers treated with CaNa2EDTA and in alcoholic patients repeatedly treated with the alcohol aversive drug Disulfiram. The mechanism of inhibition involves Cu++ chelation at the active site of DBH. The effect of CaNa2EDTA and Disulfiram on serum DBH has been compared to the effect of dithiocarbamate pesticides in vitro for the possible use of serum DBH determination for the biological monitoring of workers exposed to these pesticides. Most dithiocarbamates inhibit human serum DBH at micromolar concentrations (range of I50, 0.027-1.6 mumol/L). The inhibitory potency increased from methyl- and dimethyl dithiocarbamates to diethyl dithiocarbamates up to the most potent ethylene bisdithiocarbamates. The I50 of CaNa2EDTA was 3.8 mumol/L, higher than those of dithiocarbamates. Copper addition to the test system reactivated at stoichiometric concentrations dithiocarbamate-inhibited DBH indicating that both base line values and percent of inhibition can be calculated in a single blood sample. Results suggest that serum DBH determination could be useful in case of acute poisoning involving high doses of dithiocarbamate pesticides.


Subject(s)
Alcohol Deterrents/pharmacology , Chelating Agents/pharmacology , Disulfiram/pharmacology , Ditiocarb/pharmacology , Dopamine beta-Hydroxylase/drug effects , Edetic Acid/pharmacology , Biomarkers/blood , Dopamine beta-Hydroxylase/blood , Female , Humans , Male , Pesticides/blood
14.
J Appl Toxicol ; 14(2): 77-80, 1994.
Article in English | MEDLINE | ID: mdl-8027511

ABSTRACT

The aim of this study was to investigate the effects of single and repeated disulfiram doses on serum dopamine-beta-hydroxylase activity and blood carbon disulphide concentrations in a group of abstinent alcoholics. The increase in the blood concentration of carbon disulphide was dose dependent after the oral administration of 100-400 mg of disulfiram. Free carbon disulphide peaked at 12 h while the protein-bound fraction increased at least up to 24 h. Both single (100-400 mg p.o.) and repeated (200 mg daily p.o. for ca. 1 month) administrations failed to inhibit the activity of serum dopamine-beta-hydroxylase. The repeated daily administration of 200 mg of disulfiram also had no influence on copper-activated serum dopamine-beta-hydroxylase, which was the same before and after 1-month treatment period. Contrary to the disulfiram group, the activity of the copper-activated enzyme in the serum of abstinent alcoholics declined significantly during the same 30 days.


Subject(s)
Alcoholism/blood , Carbon Disulfide/blood , Disulfiram/pharmacology , Dopamine beta-Hydroxylase/blood , Administration, Oral , Adult , Alcoholism/enzymology , Copper/pharmacology , Disulfiram/administration & dosage , Disulfiram/antagonists & inhibitors , Dopamine beta-Hydroxylase/drug effects , Female , Humans , Male , Middle Aged , Temperance
15.
Article in Russian | MEDLINE | ID: mdl-7975996

ABSTRACT

Plasma catecholamine levels and serum dopamine-beta-hydrolase (D beta H) activity were investigated using high-performance chromatography and spectrophotometry, respectively, in 32 patients aged 10-14 with various motor pathology. Group 1 patients (21 children with spastic diplegia and clinical signs of central catecholaminergic neuromediation deficiency) received Nakom in a single daily dose 60 mg in the morning. The treatment produced a good clinical effect. Six children of group 2 with hereditary degenerative cerebral, spinal, nervous diseases and 5 children of group 3 with lower spastic paraplegia consequent to spinal cord trauma inflicted 6-12 months: before received Nakom in a single daily dose 30 mg in the morning for 14 days. The treatment in them resulted in an essential decrease of pelvic dysfunctions. All the children had a high DOPA level in blood plasma irrespective of the group and Nakom administration. Pretreatment dopamine (DA) levels were different: the least in cerebral palsy patients (0.019 +/- 0.01 ng/ml), the highest in group 2 (p < 0.05), in children with spinal cord pathology it was higher than normal and higher than in group 1 (p < 0.001). Nakom treatment promoted DA normalization in all the groups. Norepinephrine (NE) concentrations were very low in all the patients correlating with the degenerative process degree and did not change in response to Nakom administration. D beta H activity was inhibited in all the groups, especially in the spinal patients. Nakom increased both D beta H activity (p < 0.01) and motor activity. Thus, an increased DOPA level is plasma is not specific for nervous diseases.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Catecholamines/blood , Dopamine beta-Hydroxylase/blood , Movement Disorders/blood , Adolescent , Carbidopa/administration & dosage , Child , Chromatography, High Pressure Liquid , Dopamine Agonists/administration & dosage , Dopamine beta-Hydroxylase/drug effects , Drug Combinations , Female , Humans , Levodopa/administration & dosage , Male , Movement Disorders/congenital , Movement Disorders/drug therapy , Movement Disorders/etiology , Spectrophotometry
16.
Comp Biochem Physiol B ; 104(3): 567-75, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8482079

ABSTRACT

The specific adrenal dopamine-beta-hydroxylase activity measured in cat and rat was: (1) two times higher in cat than in rat; (2) significantly enhanced by ascorbate (up to 5 mM) that acts as a major activator; (3) differently affected by exogenous copper added to the incubation medium, leading to a decrease with large concentrations; and (4) similar, according to the kinetic parameters, thereby demonstrating a greater affinity for ascorbate than for tyramine.


Subject(s)
Adrenal Glands/enzymology , Cats/metabolism , Dopamine beta-Hydroxylase/metabolism , Rats, Sprague-Dawley/metabolism , Animals , Ascorbic Acid/pharmacology , Copper/pharmacology , Dopamine beta-Hydroxylase/chemistry , Dopamine beta-Hydroxylase/drug effects , Female , Hydrogen-Ion Concentration , Kinetics , Male , Rats , Species Specificity , Tyramine/pharmacology
17.
J Toxicol Sci ; 18(1): 21-9, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8386259

ABSTRACT

Selectivity of lead effect on dopamine beta-hydroxylase activity in regions of brai nfrom rats postnatally exposed to lead was tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% PbAcetate: PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6 and 8 weeks of age weight of whole brain and body in each group were measured. At the same ages activities of dopamine beta-hydroxylase and Na+K(+)-ATPase were measured in 5 brain regions of each animal. Exposure of rats to lead generally decreased Na+/K(+)-ATPase activity and showed alternative changes of dopamine beta-hydroxylase activity were detected without concomitant changes of Na+/K(+)-ATPase activity were telencephalon and pons/medulla at 2 weeks of age and telencephalon, diencephalon and pons/medulla at 4 weeks of age and midbrain and pons/medulla at 6 weeks of age and cerebellum at 8 weeks of age in rats exposed to lead at a low dose, and those in rats exposed to lead at a high dose were midbrain at 6 weeks of age and cerebellum at 8 weeks of age. These data imply that noradrenergic nervous system in the brain regions described above could selectively be affected by lead.


Subject(s)
Brain/drug effects , Dopamine beta-Hydroxylase/metabolism , Lead/toxicity , Age Factors , Animals , Brain/enzymology , Dopamine beta-Hydroxylase/drug effects , Dose-Response Relationship, Drug , Female , Male , Rats , Rats, Wistar , Sodium-Potassium-Exchanging ATPase/drug effects , Sodium-Potassium-Exchanging ATPase/metabolism
19.
Mater Med Pol ; 24(2): 85-7, 1992.
Article in English | MEDLINE | ID: mdl-1307775

ABSTRACT

The intravenous administration of ketamine hydrochloride to fifteen patients undergoing surgery produced no change in circulating plasma dopamine-beta-hydroxylase (DBH), although it produced a significant increase both in systolic blood pressure (BP) and diastolic BP during anesthesia. Halothane anesthesia that depress BP also produced no change in plasma DBH activity.


Subject(s)
Blood Pressure/drug effects , Dopamine beta-Hydroxylase/drug effects , Halothane/pharmacology , Ketamine/pharmacology , Adolescent , Adult , Child , Child, Preschool , Dopamine beta-Hydroxylase/blood , Humans , Infant , Middle Aged
20.
J Pharmacol Exp Ther ; 259(3): 1379-87, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1684822

ABSTRACT

The purpose of the present study was to determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), administered systemically or as a local infusion, has a direct neurotoxic action upon dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in BALB/c mice. Results indicated that both acute and repeated MPTP infusions (2 micrograms/0.3 microliter per side) significantly impaired locomotor activity, decreased stereotyped behavior and caused a disturbed pattern of locomotion in mice. The biochemical changes parallel the behavioral changes. Repeated MPTP infusions to the SN decreased DA levels markedly in the SN and the striatum; chronic MPTP infusions to the LC reduced NE levels markedly in the LC and the hippocampus. Furthermore, repeated MPTP injections for 7 days (30 mg/kg, one injection per day) have resulted in a long-lasting effect on both the nigral-striatal and the coeruleus-hippocampal systems. DA levels in the SN and the striatum were decreased at 1, 3, 7 and 28 days after the last MPTP injection. Similarly, NE levels in the LC and the hippocampus were also reduced markedly at the same time intervals examined. Behaviorally, repeated MPTP treatment also produced long-lasting motor deficits in mice at all time intervals studied. Moreover, the LC appeared to be more sensitive than the SN to the neurotoxic effects of MPTP. Immunohistochemical results have similarly revealed that repeated MPTP treatment markedly decreased tyrosine hydroxylase-positive cells and fibers in the SN and the LC. It also markedly decreased DA-beta-hydroxylase-positive cells and fibers in the LC.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Brain Diseases/chemically induced , Locus Coeruleus/drug effects , Substantia Nigra/drug effects , Animals , Behavior, Animal/drug effects , Biogenic Monoamines/metabolism , Brain/drug effects , Brain/enzymology , Brain/metabolism , Brain Diseases/enzymology , Brain Diseases/metabolism , Dopamine/metabolism , Dopamine beta-Hydroxylase/analysis , Dopamine beta-Hydroxylase/drug effects , Immunohistochemistry , Injections, Intraperitoneal , Locus Coeruleus/enzymology , Locus Coeruleus/metabolism , Male , Mice , Mice, Inbred BALB C , Norepinephrine/metabolism , Substantia Nigra/enzymology , Substantia Nigra/metabolism , Tyrosine 3-Monooxygenase/analysis , Tyrosine 3-Monooxygenase/drug effects
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