Papers by Werner Sieghart
Archives of Pharmacology and Therapeutics, Jan 16, 2024
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Pharmacopsychiatry, May 1, 1981
Neuroendocrine test were carried out to study effects of clomipramine treatment in 24 unipolar de... more Neuroendocrine test were carried out to study effects of clomipramine treatment in 24 unipolar depressed women. Clomipramine (50-150 mg/day) increased the response of prolactin and thyrotropin to stimulation by thyrotropin-releasing hormone (TRH), while no response of growth hormone (HGH) to TRH was seen. Clomipramine decreased the response of HGH to insulin, while the responses of prolactin and cortisol to insulin were not affected. The findings suggest that the neuroendocrine and antidepressant effects of clomipramine cannot be accounted for entirely on the basis of monoaminergic mechanisms.
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Bioorganic & Medicinal Chemistry Letters, Nov 1, 2000
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Biochemical Pharmacology, Aug 1, 2012
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Journal of Immunological Methods, Dec 1, 1986
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Neuroscience Letters, Aug 1, 1991
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European Journal of Neuroscience, Mar 1, 1997
Development of the CNS occurs as a complex cascade of pre-programmed events involving distinct ph... more Development of the CNS occurs as a complex cascade of pre-programmed events involving distinct phases of cell proliferation and differentiation. Here we show these phases correlate with cells of specific buoyant densities which can be readily accessed by density gradient fractionation. Sprague-Dawley dams were pulse-labelled with bromodeoxyuridine (BrdU) and selected regions of embryonic (E) CNS tissues at E11-22 dissociated with papain into single-cell suspensions. Proliferative cell populations were assessed by anti-BrdU and propidium iodide staining using flow cytometry. Cell differentiation was evaluated using molecular and immunocytochemical probes against mRNAs and antigens differentiating the neuroepithelial, neuronal and glial cell lineages. The results show the emergence of distinctive spatiotemporal changes in BrdU+ populations throughout the CNS during embryonic development, which were followed by corresponding changes in the cellular distributions of antigens distinguishing specific cell types. Fractionation of neocortical cells using discontinuous Percoll gradients revealed that an increasing number of cells increase their buoyancy during corticogenesis. Immunocytochemical and molecular characterization showed that the proliferative and progenitor cell populations are for the most part associated with lower buoyancy or higher specific buoyant densities (> 1.056 g/ml) whereas the post-mitotic, differentiated neurons generally separated into fractions of higher buoyancy or lower specific buoyant densities (< 1.043 g/ml). Immunostaining with antibodies against several GABAA receptor subunits (alpha 3, beta 3, gamma 2) revealed that the highest percent (70-90%) of immunopositive cells could be identified in the most buoyant, differentiating neurons found in the cortical plate/subplate regions, with the lowest percent of the immunopositive cells found in the least buoyant, proliferative and progenitor cell populations originating from the ventricular/subventricular zones. Taken together, these results indicate that buoyant density is a distinguishing characteristic of embryonic CNS cells transforming from primarily proliferative to mainly differentiating, and that fractionation of these cells according to their buoyant densities provides rapid access to the properties of specific cell lineages during the prenatal period of CNS development.
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Brain Research, Nov 1, 1976
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Journal of Neurochemistry, Nov 1, 1974
— Equilibrium or incomplete equilibrium density gradient centrifugation was used to characterize ... more — Equilibrium or incomplete equilibrium density gradient centrifugation was used to characterize the subcellular localization of exogenous [3 5S]taurine which was taken up by minces or homogenates of rat cerebral cortex. [3 5S]Taurine is accumulated in synaptosomes, which sediment more slowly than l‐[3H]norepinephrine‐accumulating particles. When [3 5S]taurine and [3H]GABA are accumulated by minces, a small difference in the sedimentation profile of taurine and GABA was observed, but no difference was found when taurine and intrasynaptosomal potassium were compared. However, potassium sedimented more slowly after incubation of homogenates than of minces. These data give evidence for the accumulation of [3 5S]taurine by a specific synaptosomal population.
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European Journal of Pharmacology, Apr 1, 1983
Membranes from cerebellum or hippocampus were incubated with various concentrations of [3H]flunit... more Membranes from cerebellum or hippocampus were incubated with various concentrations of [3H]flunitrazepam in the absence or presence of diazepam, Cl 218 872 or ethyl-beta-carboline-3-carboxylate (beta-CCE). After binding equilibrium of [3H]flunitrazepam had been established, the membranes were either filtered for determination of reversible binding or were irradiated with UV light for determination of irreversible binding. Irradiated membranes were then subjected to SDS-polyacrylamide gel electrophoresis and fluorography. Individual photolabeled proteins were identified, appropriate sections cut out of the gel, and the radioactivity in the gel pieces measured. The results indicate that [3H]flunitrazepam binding to individual benzodiazepine binding proteins and its inhibition by various drugs can be measured by the present technique and support previous evidence for the independent existence of various proteins irreversibly labeled by [3H]flunitrazepam and their possible association with different benzodiazepine receptors.
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Neuroscience Letters, Feb 1, 1989
γ-Aminobutyric acid (GABA)/benzodiazepine receptors purified from the brains of young and adult r... more γ-Aminobutyric acid (GABA)/benzodiazepine receptors purified from the brains of young and adult rats were photolabeled by [3H]flunitrazepam or [3H]muscimol. Gel electrophoresis revealed 3 different proteins with apparent molecular weight (Mr) 51,000, 53,000 and 59,000 which were specifically and irreversibly labeled by [3H]flunitrazepam and recognized by the α-subunit specific antibody bd-28. Similarly, 3 different proteins with Mrs 51,000, 53,000 and 56,000 were irreversibly labeled by [3H]muscimol and recognized by the β-subunit-specific antibody bd-17. Comparison of the photolabeling and immunological staining pattern from young and adult rats seems to indicate that proteins labeled by [3H]flunitrazepam and bd-28 are different from those labeled by [3H]muscimol and bd-17.
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Journal of Biological Chemistry, Dec 1, 2010
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Clinical Neuropharmacology, 1992
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Monatshefte Fur Chemie, 1973
Yeast mitochondria passively accumulate Co++. The quantity of Co++ taken up (5 to 43 nmoles per m... more Yeast mitochondria passively accumulate Co++. The quantity of Co++ taken up (5 to 43 nmoles per mg of mitochondrial protein) rises about linearly with the concentration of Co++ in the medium over the concentration range investigated (1.0 · 10−4 to 9.1 · 10−4 molar-Co++). The Co++ accumulation causes a small increase in the density of the mitochondria and a change in their electronmicroscopic appearance.Co++ in 3.3 · 10−5 to 1.2 · 10−4 molar concentration reversibly stimulates the respiration of intact yeast mitochondria in the presence of α-ketoglutarate. With succinate as the substrate, however, respiratory stimulation by Co++ is irreversible. When yeast mitochondria are incubated for a longer period with these amounts of Co++, respiration and oxidative phosphorylation are inhibited and DNP fails to uncouple the respiration of the mitochondria. In the presence of succinate Co++ invariably uncouples mitochondrial respiration. The presence of substrate, ADP and phosphate in addition to Co++ is obligatory for these effects to occur.In order to account for these results, at least two sites of action of Co++ in yeast mitochondria have to be considered.
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The Journal of Physiology, May 15, 2012
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Current Medicinal Chemistry, Jan 20, 2015
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British Journal of Pharmacology, Oct 1, 2000
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Clinical Chemistry, Apr 1, 1987
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Journal of Neurochemistry, Nov 1, 1981
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Journal of Neurochemistry, 1993
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Papers by Werner Sieghart