Novel synthesis of a dual fluorimetric sensor for the simultaneous analysis of levodopa and pyridoxine.

Herein, a fluorimetric sensor was fabricated based on molecularly imprinted polymers (MIPs) with two types of carbon dots as fluorophores. The MIPs produced had similar excitation wavelengths (400 nm) and different emission wavelengths (445 and 545 nm). They were used for the simultaneous analysis of levodopa and pyridoxine. First, two types of carbon dots, i.e. nitrogen-doped carbon dots (NCDs) with a quantum yield of 43%, and carbon dots from o-phenylenediamine (O-CDs) with a quantum yield of 17%, were prepared using the hydrothermal method. Their surfaces were then covered with MIPs through the reverse microemulsion method. Finally, a mixture of powdered NCD@MIP and O-CD@MIP nanocomposites was used for the simultaneous fluorescence measurement of levodopa and pyridoxine. Under optimal conditions using response surface methodology and Design-Expert software, a linear dynamic range of 38 to 369 nM and 53 to 457 nM, and detection limits of 13 nM and 25 nM were obtained for levodopa and pyridoxine, respectively. The capability of the proposed fluorimetric sensor was investigated in human blood serum and urine samples. Graphical Abstract Schematic representation of nitrogen-doped carbon dots (NCDs), carbon dots from o-phenylenediamine (O-CDs), NCDs coated with imprinted polymers (NCD@MIPs), and O-CDs coated with imprinted polymers (O-CD@MIPs) in the presence and absence of levodopa and pyridoxine.

Polypyrrole merged zirconium-based metal-organic framework NU-1000 for detection of levodopa.

A post-synthetic integration of polypyrrole onto NU-1000 MOF (PPy@NU-1000) was done by pyrrole adsorption, followed by oxidative polymerization. The synthesized materials were characterized by XRD, SEM, BET, and FTIR. The ultra-high specific surface area with high-density catalytic sites of NU-1000 (2223 m2 g-1) was combined with the electrical conductivity of PPy (2-100 S cm-1). PPy@NU-1000 provides superior electrocatalytic activity and charge transfer properties compared to an individual component. The PPy@NU-1000-modified GCE was applied to detect the biomolecule Levodopa (LD). The DPV oxidation peak of LD was strongest at 272 ± 10 mV vs. Ag/AgCl reference electrode. Under the optimized experimental condition, the fabricated electrochemical sensor exhibited a wide quantification range of 0.005-70 µM with a sub-nanomolar detection limit of 0.0001 µM (S/N 3). The described sensor exhibits high sensitivity (2.08 µA µM-1 cm-2) with reasonable stability, reproducibility, and selectivity for the detection LD in the presence of potentially interfering compounds. Furthermore, human serum analysis showed excellent recovery values within the range 99.3-101.6%. Validation of the method was performed against HPLC.Graphical abstract.

A selective colorimetric strategy for probing dopamine and levodopa through the mussel-inspired enhancement of Fe3O4 catalysis.

Mussel-inspired enhancement of Fe3O4 catalysis was discovered towards a highly selective and sensitive colorimetric strategy for the magnetic separation-based evaluation of dopamine and/or levodopa in urine, in which the specific interaction of bis-catechol-containing analytes and mesoporous Fe3O4 NPs would form highly stable complexes of bis-catechol-Fe coordination.

Point-of-care amperometric determination of L-dopa using an inkjet-printed carbon nanotube electrode modified with dandelion-like MnO2 microspheres.

An electrochemical sensor is described for the determination of L-dopa (levodopa; 3,4-dihydroxyphenylalanine). An inkjet-printed carbon nanotube (IJPCNT) electrode was modified with manganese dioxide microspheres by drop-casting. They coating was characterized by field emission scanning electron microscopy, Fourier-transform infrared spectroscopy and X-ray powder diffraction. The sensor, best operated at a working voltage of 0.3 V, has a linear response in the 0.1 to 10 µM L-dopa concentration range, a 54 nM detection limit, excellent reproducibility, repeatability and selectivity. The amperometric approach was applied to the determination of L-dopa in spiked biological fluids and displayed satisfactory accuracy and precision. Graphical abstract Schematic representation of an amperometric method for determination L-dopa. It is based on the use of inkjet-printed carbon nanotube electrode (IJPCNT) modified with manganese dioxide (MnO2).

Integrating polythiophene derivates to PCN-222(Fe) for electrocatalytic sensing of L-dopa.

Porphyrinic Metal-Organic Frameworks (porph-MOFs) are attracting attention due to the redox activity in the porphyrin subunit. Herein, we report the design of a novel core-shell structure hybrid material with a sea-cucumber morphology, namely PMeTh, containing the poly(3-methythiophene) conducting polymer coated on the surface of iron-based porph-MOFs PCN-222(Fe) via in-situ oxidative chemical polymerization. The porous PCN-222(Fe) serves as the electrocatalytic sites, while the poly(3-methythiophene) conducting polymer functions as the charge collector to facilitate the charge transport to the redox active sites. The resulting PMeTh composite demonstrates an excellent electrochemical response towards the levodopa detection. The sensitivity towards the L-dopa detection is estimated to be 1.868 µA ⋅ µM-1 ⋅ cm-2 in the linear concentration of 0.05-7.0 µmol ⋅ L-1 and 0.778 µA ⋅ µM-1 ⋅ cm-2 in the linear concentration of 7.00-100 µmol ⋅ L-1, respectively. Additionally, the levodopa sensor exhibits a low detection limit of 2 nmol L-1 as well as excellent stability after 120 cycles in 10 µmol L-1 levodopa. The feasibility of this novel L-dopa sensor was evaluated in human urine samples by standard addition. The satisfactory recoveries were in the range of 97.0-104.5% with the R.S.D. value lower than 4.4%. The method of intergrating porph-MOFs and conducting polymers can efficiently expand the porph-MOFs based composites in bioanalysis.

Simultaneous voltammetric sensing of levodopa, piroxicam, ofloxacin and methocarbamol using a carbon paste electrode modified with graphite oxide and ß-cyclodextrin.

A carbon paste electrode (CPE) was modified with graphite oxide (GrO) and ß-cyclodextrin (CD) to obtain a sensor for simultaneous voltammetric determination of levodopa (LD), piroxicam (PRX), ofloxacin (OFX) and methocarbamol (MCB). The morphology, structure and electrochemical properties of the functionalized GrO were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, contact angle measurements and cyclic voltammetry. Under the optimal experimental conditions, the sensor is capable of detecting LD, PRX, OFX and MCB by square wave voltammetry (SWV) at working potentials of +0.40, +0.60, +1.03 and + 1.27 V (versus Ag/AgCl), respectively. Response is linear from 1.0 to 20 µM for LD, from 1.0 to 15 µM for PRX, from 1.0 to 20 µM for OFX, and from 1.0 to 50 µM for MCB. The respective limits of detection are 65, 105, 89 and 400 nM. The method was successfully applied to the simultaneous determination of LD, PRX, OFX and MCB in (spiked) real river water and synthetic urine samples, and the results were in agreement with those obtained using a spectrophotometric method, with recoveries close to 100%. Graphical abstract Schematic presentation of a novel electroanalytical method employing a carbon paste electrode modified with graphite oxide and ß-cyclodextrin for the simultaneous determination of levodopa, piroxicam, ofloxacin and methocarbamol in urine and river water samples by square wave voltammetry.

Substantial renal conversion of L-threo-3,4-dihydroxyphenylserine (droxidopa) to norepinephrine in patients with neurogenic orthostatic hypotension.

BACKGROUND: The pressor effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa, Northera™) results from conversion of L-DOPS to norepinephrine (NE) in cells expressing L-aromatic-amino-acid decarboxylase (LAAAD). After L-DOPS administration the increase in systemic plasma NE is too small to explain the increase in blood pressure. Renal proximal tubular cells abundantly express LAAAD. Since NE generated locally in the kidneys could contribute to the pressor effect of L-DOPS, in this study we assessed renal conversion of L-DOPS to NE. METHODS: Ten patients who were taking L-DOPS for symptomatic orthostatic hypotension had blood and urine sampled about 2 h after the last L-DOPS dose. L-DOPS and NE were assayed by alumina extraction followed by liquid chromatography with electrochemical detection. Data were compared in patients off vs. on levodopa/carbidopa. RESULTS: In patients off levodopa/carbidopa the ratio of NE/L-DOPS in urine averaged 63 times that in plasma (p = 0.0009 by t test applied to log-transformed data). In marked contrast, in the three patients on levodopa/carbidopa the ratio of NE/L-DOPS in urine did not differ from that in plasma. CONCLUSION: There is extensive renal production of NE from L-DOPS. Carbidopa seems to attenuate the conversion of L-DOPS to NE in the kidneys. Further research is needed to assess whether the proposed paracrine effect of L-DOPS in the kidneys contributes to the systemic pressor response.

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na+, K+-ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload.

An electrochemical biosensor based on nanoporous stainless steel modified by gold and palladium nanoparticles for simultaneous determination of levodopa and uric acid.

In this paper, an electrochemical biosensor based on gold and palladium nano particles-modified nanoporous stainless steel (Au-Pd/NPSS) electrode has been introduced for the simultaneous determination of levodopa (LD) and uric acid (UA). To prepare the electrode, the stainless steel was anodized to fabricate NPSS and then Cu was electrodeposited onto the nanoporous steel by applying the multiple step potential. Finally, the electrode was immersed into a gold and palladium precursor's solution by the atomic ratio of 9:1 to form Au-Pd/NPSS through the galvanic replacement reaction. Morphological aspects, structural properties and the electroanalytical behavior of the Au-Pd/NPSS electrode were studied using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), electrochemical impedance spectroscopy (EIS) and voltammetric techniques. Also, differential pulse voltammetry (DPV) was used for the simultaneous determination of LD and UA. According to results, the surface of Au-Pd/NPSS electrode contained Au and Pd nanoparticles with an average diameter of 75nm. The electrode acted better than Au/NPSS and Pd/NPSS electrodes for the simultaneous determination of LD and UA, with the peak separation potential of about 220mV. Also, the calibration plot for LD was in two linear concentration ranges of 5.0-10.0 and 10.0-55.0µmolL(-1) and for UA, it was in the range of 100-1200µmolL(-1). The detection limit for LD and UA was 0.2 and 15µmolL(-1), respectively. The modified electrode had a good performance for LD and UA detection in urine, blood serum and levodopa C-Forte tablet.

Size-dependent active effect of cadmium telluride quantum dots on luminol-potassium periodate chemiluminescence system for levodopa detection.

It was found that cadmium telluride (CdTe) quantum dots (QDs) with different sizes can have a great sensitizing effect on chemiluminescence (CL) emission from luminol-potassium periodate (KIO4) system. Levodopa, a widely prescribed drug in the treatment of Parkinson's disease, could inhibit luminol-KIO4-CdTe QDs CL reaction in alkaline solution. The inhibited CL intensity was proportional to the concentration of levodopa in the range from 8.0 nM to 10.0 µM. The detection limit was 3.8 nM. This method has been successfully applied to determine levodopa in pharmaceutical preparation and human urine and plasma samples with recoveries of 94.1-105.4%. This was the first work for inhibition effect determination of levodopa using a QD-based CL method.

Renalase regulates renal dopamine and phosphate metabolism.

Renalase is a kidney-secreted catecholamines-degrading enzyme whose expression and activity are downregulated by increased dietary phosphate. A renalase knockout (KO) mouse model was used to explore the mechanisms mediating renalase's effect on phosphate excretion. Compared with wild-type (WT) mice maintained on a regular diet, KO mice show decreased serum PO4(-) (KO = 5.3 ± 0.2 vs. WT = 6.0 ± 0.1, n = 6; P < 0.04) and increased urinary PO4(-) excretion (urine PO4(-)/creatinine: KO = 7.7 ± 0.3 vs. WT = 6.1 ± 0.3, n = 6; P < 0.02). However, both WT and KO mice respond similarly to PO4(-) restriction by increasing renal COMT-1 activity and markedly decreasing PO4(-) excretion, which excludes an intrinsic renal defect in the KO. Renal sodium-phosphate cotransporter Npt2a, sodium proton exchanger NHE3 expression, and MAO-A and B activity did not differ between WT and KO. Only catechol-O-methyl transferase (COMT) expression and activity were significantly increased in KO mice. Despite that, urinary dopamine increased by twofold, whereas urinary l-DOPA excretion decreased by twofold in the KO mouse, indicating an upregulation of renal dopamine (DA) synthesis. These data indicate that renalase deficiency is associated with increased renal DA synthesis, stimulated PO4(-) excretion, and moderately severe hypophosphatemia. The signal to increase renal DA synthesis is strong since it overcomes a compensatory increase in COMT activity.

Biomimetic sensor for certain catecholamines employing copper(II) complex and silver nanoparticle modified glassy carbon paste electrode.

A dimeric Cu(II) complex [Cu(µ(2)-hep)(hep-H)](2)·2ClO(4) (1) containing bidentate (hep-H=2-(2-hydroxyethyl)pyridine) ligand was synthesized and characterized by single crystal X-ray diffraction studies. Each Cu-ion in 1 is in a distorted square pyramidal geometry. Further 1 along with silver nanoparticles (SNPs) have been used as modifier in the construction of a biomimetic sensor (1-SNP-GCPE) for determining certain catecholamines viz., dopamine (DA), levodopa (l-Dopa), epinephrine (EP) and norepinephrine (NE) using cyclic voltammetry, chronocoulometry, electrochemical impedance spectroscopy and adsorptive stripping square wave voltammetry (AdSSWV). Finally, the catalytic properties of the sensor were characterized by chronoamperometry. Employing AdSSWV, the calibration curves showed linear response ranging between 10(-6) and 10(-9)M for all the four analytes with detection limits (S/N=3) of 8.52×10(-10)M, 2.41×10(-9)M, 3.96×10(-10)M and 3.54×10(-10)M for DA, l-Dopa, EP and NE respectively. The lifetime of the biomimetic sensor was 3 months at room temperature. The prepared modified electrode shows several advantages such as simple preparation method, high sensitivity, high stability, ease of preparation and regeneration of the electrode surface by simple polishing along with excellent reproducibility. The method has been applied for the selective and precise analysis of DA, l-Dopa, EP and NE in pharmaceutical formulations, urine and blood serum samples.

Fluorescence assay of catecholamines based on the inhibition of peroxidase-like activity of magnetite nanoparticles.

We report a fluorescence approach for the highly selective and sensitive detection of catecholamines using magnetite nanoparticles (Fe(3)O(4) NPs) in the presence of Amplex UltraRed (AUR) and H(2)O(2). Fe(3)O(4) NPs catalyze H(2)O(2)-mediated oxidation of AUR. The resulting product fluoresces (excitation/emission maxima, ca. 568/587nm) more strongly, relative to AUR. When catecholamines bind to Fe(3)O(4), the complexes that are formed induce decreased activity of Fe(3)O(4) NPs, mediated through the coordination between Fe(3+) on the NP surface and the catechol moiety of catecholamines. As a result, Fe(3)O(4) NPs-catalyzed H(2)O(2)-mediated oxidation of AUR is inhibited by catecholamines. The limits of detection for dopamine (DA), L-DOPA, norepinephrine, and epinephrine were 3 nM, 3 nM, 3 nM, and 6 nM, respectively. The Fe(3)O(4) NPs-H(2)O(2)-AUR probe exhibited high selectivity (>1000-fold) toward catecholamines over other tested biomolecules that commonly exist in urine. Four catecholamines had similar sensitivity because the inhibition of the Fe(3)O(4) NPs activity relies on the presence of the catechol moiety. This approach also allowed the determination of tyrosinase activity because tyrosinase catalyzes the conversion of l-tyrosine to L-DOPA. We validated the practicality of the use of the Fe(3)O(4) NPs-H(2)O(2)-AUR probe for the determination of the concentrations of DA in urine samples.

Simultaneous spectrofluorimetric determination of levodopa and propranolol in urine using feed-forward neural networks assisted by principal component analysis.

The simultaneous determination of levodopa (LD) and propranolol (PRO) using fluorescence spectrometric technique is described. The method involves measuring the natural fluorescence of these drugs in the micellar media of sodium dodecyl sulfate (SDS) using principal component analysis-feed-forward neural networks (PC-FFNNs). Experimental conditions such as effect of pH and SDS concentration were optimized. Under the optimum conditions, the linear determination ranges of LD and PRO are 2.0 x 10(-8) to 1.0 x 10(-5)mol L(-1) and 3.6 x 10(-9) to 1.8 x 10(-6)mol L(-1), respectively. A set of synthetic binary mixtures of LD and PRO was prepared and their concentrations were predicted by the proposed method. Satisfactory results were obtained by the combination of fluorescence technique with chemometrics methods. The method was successfully applied to the determination of LD and PRO in tap water and in urine samples.

Simultaneous determination of levodopa and carbidopa by synchronous fluorescence spectrometry using double scans.

A synchronous fluorescence spectrometric method is described for the simultaneous determination of binary mixtures of levodopa and carbidopa in pharmaceutical formulation and urine sample, without prior separation steps, using two scans. At Delta lambda = 30 nm, only carbidopa yields a detectable signal that is independent of the presence of levodopa. Similarly, at Delta lambda = 65 nm the signal of levodopa is not influenced by the presence of carbidopa. Signals at two wavelengths, 288 nm (Delta lambda = 30 nm) and 281 nm (Delta lambda = 65 nm), vary linearly with carbidopa and levodopa concentrations over the range 0.019-1.971 microg mL(-1) (for levodopa) and 0.022-2.262 microg mL(-1) (for carbidopa), respectively. The correlation coefficients for the standard calibration graphs were 0.9962 and 0.9951 (n=10) for carbidopa and levodopa, respectively. The limits of detection (LOD estimated as per IUPAC recommendations) were 0.01 and 0.006 microg mL(-1) for carbidopa and levodopa, respectively. The method was successfully applied to the determination of levodopa and carbidopa in pharmaceutical formulation and urine sample. The recovery results were satisfactory.

Development of a sensitive flow-injection-chemiluminescence detection method for the determination of levodopa.

A simple chemiluminometric method using flow injection has been developed for the determination of levodopa, based on its sensitizing effect on the weak chemiluminescence (CL) reaction between Na(2)SO(3) and acidic KMnO4. Under optimum experimental conditions, the CL intensity was linearly related to the concentration of levodopa from 3.4 x 10(-8) to 2.4 x 10(-5) mol/L and the detection limit was 1.1 x 10(-8) mol/L (s:n = 3). The relative standard deviation (RSD) of the proposed method calculated from 20 replicate injection of 3 x 10(-7) mol/L levodopa was 3.3%. The correlation coefficient was 0.997. The method was successfully applied to the determination of levodopa in commercial pharmaceutical formulations and spiked urine samples.

Determination of levodopa and biogenic amines in urine samples using high-performance liquid chromatography.

A chromatographic system is developed for the separation and determination of levodopa, biogenic amines, and their metabolites from the catecholamines group: dopamine (DA), epinephrine (E), normetanephrine (NMN), metanephrine (MN), 3,4-dihydroxyphenylacetic acid (DOMA), 3-metoxy-4-hydroxyphenyl-glycol (MHPG), and homovanillic acid (HVA); and indoloamines group: serotonin (5HT) and 5-hydroxyindole-3-acetic acid (5HIAA) in urine. The limit of detection (LOD) and limit of quantitation (LOQ) are determined for all compounds with signal-to-noise ratio (S/N) of 3 and 10, respectively. LOD 10 (ng/mL) and LOQ 30 (ng/mL) are determined for L-DOPA, DOMA, E, NMN, DA, MN, and MHPG, as well as LOD 8 (ng/mL) and LOQ 24 (ng/mL) for HVA, 5HT, and 5HIAA. A fluorescence detector is used. Gradient elution with acetate buffer (pH=4.66) with methanol is applied. In urine samples from patients treated with levodopa, the following concentrations (microg/mL) of analytes are determined: L-DOPA 3.73-46.80, DOMA 1.43-28.43, E 0.83-13.57, NMN 2.58-8.81, DA 24.07-62.11, MN 0.89-66.20, MHPG 6.72-63.64, 5HT 22.96-95.27, 5HIAA 1.45-14.77, and HVA 0.21-15.07.

Determination of catecholamines by flow-injection analysis and high-performance liquid chromatography with chemiluminescence detection.

A chemiluminescence (CL) detection of catecholamines [norepinephrine (NE), epinephrine (E), dopamine (DA) and L-dopa (LD)] is described for the flow-injection (FI) and high-performance liquid chromatographic (HPLC) determination of these compounds. The detection method is based on the inhibition effect of catecholamines (CAs) on the CL reaction of luminol with iodine in the alkaline medium. The proposed FI method allows the determination of CAs in pharmaceutical preparations for the purpose of drug quality control. The calibration curves show good linearity in the concentration range of: 1.1-20.0 microg l(-1) (NE), 0.5-5.0 microg l(-1) (E), 0.6-9.0 microg l(-1) (DA) and 0.6-10.0 microg l(-1) (LD). The limits of detection (defined as a signal-to-noise ratio of 3) are: 0.34 microg l(-1) (NE), 0.15 microg l(-1) (E) and 0.18 microg l(-1) (DA, LD). The HPLC procedure was successfully applied for the determination of catecholamines (NE, E, DA) in human urine after solid-phase extraction (SPE). In a simple run time CAs can be determined in 20 min. The chromatographic linear ranges are: 5.0-72.0 microg l(-1) (NE), 5.0-48.0 microg l(-1) (E) and 5.0-96.0 microg l(-1) (DA). The limits of detection for three urinary CAs are: 0.71 microg l(-1) (NE), 0.26 microg l(-1) (E) and 0.73 microg l(-1) (DA).

Rapid analysis of L-dopa in urine samples using gold nanoelectrode ensembles.

This work describes the application of a three-dimensional gold nanoelectrode ensembles (GNEE) for monitoring L-dopa in standards and human urine samples using flow injection analysis (FIA) with amperometric detection. Analytical results reveal that the GNEE exhibited better electrocatalytic activity than a gold disk or glassy carbon electrode. Under optimal conditions of L-dopa analysis at GNEE, the calibration plot has a linear range of 5-300 ng/mL with a coefficient of variation (CV) of 3.1% in pH 7.0 phosphate buffer saline (PBS, pH 7.0). The detection limit was 3.0 ng/mL for FIA. The high precision and sensitivity of GNEE provides a feasible means of directly determining l-dopa in urine samples.

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy.

The present study evaluated the possible role of the renal dopaminergic system in the sodium retention of HgCl2-induced nephrotic syndrome. The time courses of urinary excretion of sodium, protein, dopamine and the precursor l-3,4-dihydroxyphenylalanine (L-Dopa) were evaluated in HgCl2-treated and control rats up to day 21. The renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine, was evaluated during negligible proteinuria accompanied with enhanced sodium retention (day 7), increased proteinuria accompanied with greatest sodium retention (day 14) as well as during increased proteinuria accompanied with negative sodium balance (day 21). Also, the influence of volume expansion (VE, 5% bw) and the effects of the D1-like agonist fenoldopam (10 microg kg bw(-1) min(-1)) on natriuresis and on proximal tubular Na+,K+-ATPase activity were examined on day 14. The daily urinary dopamine output and urinary dopamine/L-Dopa ratios were reduced in HgCl2-treated rats from day 2 and beyond. This was accompanied by a marked decrease in renal AADC throughout the study. During VE, the fenoldopam-induced inhibition of proximal tubular Na+,K+-ATPase activity was similar between HgCl2-treated and control rats. However, the urinary sodium excretion during fenoldopam infusion was markedly increased by 60% to 120% in control rats but was not altered in HgCl2-treated rats. It is concluded that HgCl2 nephrosis is associated with a blunted renal dopaminergic system activity. However, the lack of renal dopamine in HgCl2 nephrosis does not appear to be related with the overall renal sodium retention in a state of proteinuria.