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Biomedical subjects

D Neuser

Publications and source records attributed to D Neuser.

At least 37 records · Page 2Linked to original sources
PubMed1989

Endothelin stimulates release of atrial natriuretic peptides in vitro and in vivo.

The effect of endothelin (END) on the release of atrial natriuretic peptides (ANP) was studied in isolated rat atria and in conscious rats. END stimulates the ANP release in vitro in a dose-dependent manner. An increase in ANP plasma levels and cyclic GMP plasma levels was also observed in conscious rats after injection of END. When a monoclonal antibody directed against ANP was injected together with END the increase in cyclic GMP was completely blocked. From this study it is concluded that END is a potent secretagogue for ANP both in vitro and in vivo.

Animals↗
PubMed1989

Autoradiographic localization of [125I]endothelin-1 and [125I]atrial natriuretic peptide in rat tissue: a comparative study.

The autoradiographic localization of [125I]endothelin-1 (ET-1) and [125I]atrial natriuretic peptide (ANP) after i.v. administration has been investigated in rats. Labeled peptides are rapidly distributed to tissues and peripheral organs. After administration of [125I]ET-1 (1-21), the highest enrichment of radioactivity was found in the lung, kidney, liver, adrenal gland, and heart. After administration of [125I]ANP (1-28), the highest levels of radioactivity could be observed in the kidney, adrenal gland, and endocardium. Compared to blood levels in both cases, a relative enrichment of radioactivity is also found in the vascular wall of the aorta. For ANP, no distribution of radioactivity in the lung could be observed. Other organs, especially the kidney and the adrenal gland, showed a similar distribution pattern with respect to substructures.

Animals↗
PubMed1989

Autoradiographic localization of 125J-endothelin in rat tissues.

A potent peptidergic vasoconstrictor in vitro and in vivo termed endothelin has been isolated from the supernatant of cultured endothelial cells. The autoradiographic localization of 125J-endothelin has been studied after intravenous administration in rat tissues. Highest enrichment of radioactivity was found in kidney and lung. Activity was also detected, especially in vascular wall of the aorta and adrenal gland.

Animals↗
PubMed1988

Modulation of atrial natriuretic peptide-induced cGMP accumulation by [Arg8]vasopressin in the cultured renal epithelial cell line, LLC-PK1.

Atrial natriuretic peptide (ANP) III stimulated the formation of intracellular cGMP in renal epithelial cells (LLC-PK1) dose dependently. Incubation of LLC-PK1 cells with [Arg8]vasopressin resulted in an increase in intracellular cAMP levels. The stimulatory effect of ANP III on the cyclic cGMP system was inhibited by coincubation with [Arg8]vasopressin in a dose-dependent manner.

Arginine Vasopressin↗
PubMed1988

The reduction of renin and aldosterone as a response to acute hypervolemia is blocked by a monoclonal antibody directed against atrial natriuretic peptides.

We have previously reported that the strong diuresis, natriuresis and urinary cyclic GMP excretion after acute volume loading in rats are caused by ANP and can be blocked by additionally given monoclonal antibodies directed against ANP. The present report describes that in contrast to the changes in ANP and cyclic GMP, the plasma renin activity and aldosterone concentration are decreased after volume loading. This decrease is completely blocked by simultaneous administration of the monoclonal antibodies. Plasma cyclic AMP levels are not affected. From this study it seems to be clear that the inhibition of the renin-aldosterone system is not a direct effect of volume expansion but is specially mediated by the released ANP.

Aldosterone↗
PubMed1988

Biosynthesis of 18-hydroxydeoxycorticosterone and corticosterone in adrenal tissue of rat strains with salt-dependent hypertension.

Biosynthetic patterns of 18-OH-deoxycorticosterone (18-OH-DOC) and corticosterone (B) in adrenal tissue of Wistar-rats and two rat strains with salt-dependent hypertension (Dahl-, Sabra-rats) were measured by means of quantitative HPLC-analysis. The relative activity of 18-hydroxylation is expressed as the ratio 18-OH-DOC/18-OH-DOC + B, in the following called Q. Wistar-rats show a constant product ratio Q of 0.40 +/- 0.01. Dahl-rats, however, exhibit typical differences between the two substrains. Adrenal tissue of salt-resistant (Dahl-R) rats produces significantly less 18-OH-DOC than tissue from salt-sensitive (Dahl-S) rats: Q = 0.17 +/- 0.01 (Dahl-R) vs. Q = 0.37 +/- 0.01 (Dahl-S). No such difference was observed between the two Sabra-substrains. This indicates, that other mechanisms than an altered 11 beta-18-hydroxylation are involved in the salt-dependent hypertension of Sabra-rats.

Adrenal Glands↗
PubMed1988

Modulation of ANP receptor-mediated cGMP accumulation by atrial natriuretic peptides and vasopressin in A10 vascular smooth muscle cells.

ANP receptor binding and desensitization were demonstrated in the A10 vascular smooth muscle cell (VSMC) line. Concomitantly, the ANP receptor coupled guanylate cyclase activity was reduced by the receptor down-regulation with ANP. The ANP stimulated cGMP accumulation is modulated by arginine-vasopressin, while the arginine-vasopressin mediated cAMP system remained unaffected by ANP. Results suggest negative coupling of arginine-vasopressin receptors to the guanylate cyclase activity, and indicate that the vasorelaxant activity of ANP might be regulated in part by arginine-vasopressin via specific receptor sites.

Animals↗
PubMed1988

4,4-Diphenylpiperidine derivates and their sila analogues. A comparative study of their interaction with neural receptor biding sites and synaptosomal monoamine uptake.

The potential anti-Parkinson drugs 1-R-4,4-diphenylpiperidines and 1-R-4,4-diphenyl-4-sila-piperidines (R = H, CH3, i-propyl and t-butyl) were evaluated for their neuroreceptor affinity with respect to their structure-activity relationship. In these compounds substitution of the central carbon at position 4 by a silicon leads to more lipophilic substances. While the binding of these compounds to dopamine, serotonin and gamma-aminobutyric acid/benzodiazepine receptors is relatively non-specific, the binding to the mu- and delta-subtypes of opiate receptors and to the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine receptor binding site show probably pharmacologically relevant effects. In almost all cases the sila-compounds have a slightly higher receptor affinity than the corresponding carbon-compounds. The studies on the uptake sites for the biogenic amines noradrenaline, dopamine and serotonin, on the other hand, reveal some considerable differences between the carbon- and silicon-containing analogues. The 4,4-diphenyl-4-sila-piperidine has much stronger uptake inhibiting properties for noradrenaline and serotonin than the corresponding carbon compound.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

The use of a monoclonal antibody for the determination of atrial natriuretic peptides in human plasma.

A monoclonal antibody (mab) directed against alpha-human atrial natriuretic peptides (alpha-hANP) was produced. Using this mab a radioimmunoassay for the determination of hANP-like immunoreactivity in human plasma was established. To demonstrate the possible application of this radioimmunoassay for clinical diagnosis, plasma levels were measured in healthy subjects and in patients with renal failure before and after hemofiltration or hemodialysis. Plasma levels in healthy subjects ranged between less than 30 and 124 pg/ml. Mean plasma concentrations of hANP-IR in uremic subjects were 324 pg/ml before and 113 pg/ml after hemofiltration or hemodialysis.

Adult↗
PubMed1987

Alpha-h-ANP is the only form of circulating ANP in humans.

Alpha-human atrial natriuretic peptide (alpha-h-ANP) was purified to homogeneity from human plasma of healthy adults in a three-step procedure including immunoaffinity chromatography on immobilized monoclonal anti-alpha-h-ANP antibody (moab). A single peak of immunoreactivity was obtained after final reversed-phase HPLC and the amino acid sequence of the isolated material was identical to that of synthetic alpha-h-ANP. No further atrial peptides could be detected although the moab reacts with all biologically active peptides. It is therefore concluded that alpha-h-ANP is the only form of ANP circulating in human plasma.

Adult↗
PubMed1987

Blockade of the response to volume expansion by monoclonal antibodies against atrial natriuretic peptides.

It is known that plasma levels of atrial natriuretic peptides (ANP) increase in response to volume expansion. However, the extent to which these increased levels of ANP participate in the renal response to volume expansion remained unknown. This question can be answered with the aid of a monoclonal antibody that binds specifically to the biologically active forms of ANP: Ascitic fluid containing this monoclonal antibody dose-dependently and specifically blocks the natriuretic, diuretic and hypotensive effects of synthetic atriopeptin II given intravenously in rats. Volume expansion induced by injection of 20 ml/kg homologous blood in anaesthetized rats evokes massive diuresis and natriuresis. Pretreatment with ascitic fluid containing monoclonal antibody completely blocks this diuretic and natriuretic response during the first 20 min after volume expansion. Thus the initial renal response to volume expansion is due to the increase in endogenous ANP. Similar results were obtained for volume expansion with isotonic saline in conscious rats. It is supposed that the effects of ANP are mediated through particulate guanylate cyclase activation and intracellular cyclic guanosine-monophosphate (cGMP) accumulation in target tissues including renal and vascular smooth muscles cells. Besides increasing plasma ANP levels (measured by radioimmunoassay) volume expansion also induces an increase of cGMP levels both in plasma, urine and in renal tissue. This increase is ANP-dependent as it can be blocked by the monoclonal antibody.

Animals↗
PubMed1986

Receptor binding, cGMP stimulation and receptor desensitization by atrial natriuretic peptides in cultured A10 vascular smooth muscle cells.

Receptor characteristics for atrial natriuretic peptides (ANP) were demonstrated in the permanent tissue culture system of vascular smooth muscle cell (VSMC) line. 125I-ANP exhibited reversible and saturable binding to A10 rat VSMC, and the equilibrium dissociation constant, Kd was 157 pM and maximal binding capacity, Bmax amounted to 115 fmol/mg of protein. Binding of the 125I-ligand was highly specific for certain potently displacing ANP analogues with inhibition constants (Ki values) in the nano- or even subnanomolar concentration range. Pretreatment of VSMC with ANP yielded receptor desensitization to one half of the ANP receptor density, and supports the conclusion of receptor autoregulation by ANP in A10 VSMC. The receptor coupled intracellular cGMP system was stimulated, and thus demonstrates the application of A10 cells as a model for the study of ANP receptor interaction involved in vascular smooth muscle relaxation.

Animals↗
PubMed1986

The use of a monoclonal antibody to measure plasma atriopeptins in rat.

A monoclonal antibody with specificity for atrial natriuretic peptides (ANP) was produced, that can be used for the radioimmunological determination of ANP-immunoreactivity (ANP-IR) in rat plasma. The antibody recognizes atriopeptin I, II, III, as well as alpha-hANP and alpha-hANP fragment (7-28) and does not crossreact with ANP-fragments (13-28) and (18-28). Plasma levels of ANP-IR in conscious Wistar rats were determined before and after volume-loading. Basal plasma levels of ANP-IR were 108 +/- 12 pg/ml, and after volume-loading increased to 800 +/- 59 pg/ml.

Animals↗
PubMed1985

Effect of tocainide on the concentrations of norepinephrine dopamine, serotonin and histamine in rat brain and its binding affinity to neuroceptors.

Tocainide (W-36095, Xylotocan) is a derivative of lidocaine which is applied clinically as a cardiac antiarrhythmic. In addition, it diminishes the severity of symptoms in neurological disorders such as myotonia and paramyotonia and in patients with torticollis spasmodicus it brings about a distinct reduction in the tension of the neck muscles. It was investigated whether in reducing the tonus in torticollis spasmodicus tocainide could be acting on the central nervous system. The binding affinity of the substance to the dopamine, serotonin, opiate, GABA and benzodiazepine receptors was measured without finding any significant affinities. In addition, the effect of tocainide on the concentration of the neurotransmitters norepinephrine (noradrenaline), dopamine, serotonin and histamine were investigated in rat brain, and it was found that tocainide induces a significant increase in dopamine and serotonin concentrations. This lead to the conclusion that, in addition to its antiarrhythmic effects, tocainide acts on the central nervous system.

Animals↗
PubMed1984

Development and properties of a monoclonal antibody specific for human ecto-5'-nucleotidase.

After immunization with purified human placental ecto-5'-nucleotidase and fusion, 18 different hybrids were obtained which produce an antibody inhibitory for enzyme activity. These antibodies show complete cross-reactivity with the enzyme in a membrane-bound form or on the surface of intact cells. After cloning and ascites production, the antibody of one clone ( IFH - 5N1 ) was studied in greater detail. The IFH - 5N1 antibody is of the IgG 1 subclass. Optimal enzyme inhibition is 90% for purified 5'-nucleotidase and 80% for the enzyme on lymphoblasts. The specificity of this antibody is further demonstrated by enzyme inhibition assays and fluorescence labeling using various 5'-nucleotidase-positive and -negative human cells such as peripheral blood lymphocytes, leukemic cells, lymphoblastoid B- and T-cell-lines and fibroblasts. The antibody should provide a useful tool for the diagnosis of certain forms of acute leukemias and for the study of normal human lymphocyte subpopulations.

5'-Nucleotidase↗
PubMed1984

Beta-endorphin-, leucine enkephalin- and methionine enkephalin-like immunoreactivity in human cerebrospinal fluid. Simultaneous determination and relation to neurological disorders.

beta-Endorphin, leucine enkephalin and methionine enkephalin, were measured in 41 samples of human lumbar cerebrospinal fluid (CSF) of patients with different neurological diseases. beta-Endorphin-like immunoreactivity (beta-ELI) was present in concentrations between 10 and 150 fmol/ml CSF, and in 30 of the 41 samples studied the levels ranged from 10 to 40 fmol/ml. Methionine enkephalin-like immunoreactivity (MELI) measured 1-85 pmol/ml CSF, with 24 of the 41 samples having values between 3 and 4 pmol/ml. CSF concentrations of leucine enkephalin-like immunoreactivity (LELI) ranged from 0.1 to 12.5 pmol/ml, and in 31 of the 41 CSF samples studied LELI was present in concentrations of 0.1-0.25 pmol/ml. No significant relationship exists between the concentrations of beta-endorphin in CSF and sex and age of patients, CSF protein, CSF IgG and CSF leukocytes. No interrelationship could be found between beta-ELI, MELI and LELI concentrations.

Adolescent↗
PubMed1983

The interactions of 1-alkyl-4,4-diphenylpiperidines with opiate receptors.

1-Alkyl-4,4-diphenylpiperidines inhibit the binding of mu- and delta-opiate receptor agonists to crude synaptosomal membranes of rat brain. Opiate receptor affinity is dependent on the nature of the 1-alkyl substitution. In displacing [3H]etorphine, [3H]dihydromorphine and [3H][D-Ala2,D-Leu5] enkephalin, the 1-methyl-derivative was most effective (IC50 [3H]etorphine = 9 microM, IC50 [3H]dihydromorphine = 0.71 microM, IC50 [3H][D-Ala2,D-Leu5]enkephalin = 2.1 microM). 1-t-Butyl-4,4-diphenylpiperidine and its 1-isopropyl analogue, used as antiparkinsonism drugs, exhibit distinctly lower inhibiting concentration values (50% inhibition, IC50 values).

Animals↗