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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 246 (1963), S. 203-214 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung 2 Tage nach Injektion von H-3-Dopa wurde in mit α-Methyl-Dopa vorbehandelten Melanom-Mäusen (Melanosarkom, Typ Harding-Passey) die H-3-Aktivität in Melanom, Nebenniere, Magen und Leber gemessen. Die Hemmung der Dopa-Decarboxylase mit α-Methyl-Dopa steigert im Melanom die Bildung von H-3-markiertem Melanin auf den 3- bis 4fachen Wert, während sie ohne Einfluß auf den H-3-Brenzcatechinamin-Gehalt der Nebenniere ist. Dieser Effekt wird durch den langsameren Abbau des Dopa in den behandelten Tieren erklärt. Die feingewebliche Verteilung der H-3-Aktivität in Melanom, Nebenniere, Magen und Leber, wurde autoradiographisch untersucht. In Melanocyten und Melanophagen sowie in den chromaffinen Zellen von Nebenniere und Magen wurde die H-3-Aktivität stark angereichert.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 373-386 
    ISSN: 1432-1912
    Keywords: Kidney ; Renal Handling ; Dopamine ; Noradrenaline ; Adrenaline ; Catechol-O-Methyl-Transferase (COMT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 12 female dogs renal excretion and catabolism of 14C-(±)-adrenaline, 14C-(±)-noradrenaline, 14C-dopamine and 3H-(±)-normetanephrine were investigated using a modified stop-flow technique. Radioactive compounds were infused, together with inulin, into the left renal artery for 10 min. During the first 2 min of the infusion period the left ureter was occluded. Urine samples were serially collected from both kidneys up to the end of the infusion. In the urine the total radioactivity and the pattern of radioactive metabolites were measured. On average, the infused kidney excreted from the infused dose of 14C-adrenaline 9.4% as adrenaline, 27.9% as metanephrine and 5.8% as deaminated or conjugated metabolites. From infused 14C-noradrenaline 7.4% was excreted as noradrenaline, 3.5% as normetanephrine and 1% as deaminated or conjugated compounds. When 3H-normetanephrine was infused the urine contained only radioactive normetanephrine (22.2%). From the infused dose of 14C-dopamine 9.6% was excreted as dopamine, 16.2% as 3-O-methyldopamine and 3.7% as deaminated or conjugated compounds. — Urine from the other kidney contained 1/25 to 1/5 the radioactivity of that from the infused side, but the pattern of radioactive compounds was similar. From the excretion rate of simultaneously infused inulin the filtration fraction of the infused kidney was determined. That part of the infused 14C-catecholamines which was excreted unmetabolized in the urine, corresponds to the filtration fraction in this kidney. Therefore, it is suggested, that in mammals the unmetabolized catecholamines of the urine are mainly excreted by glomerular filtration and not by tubular secretion. On the other hand, the urinary O-methylated radioactive catecholamines, which were excreted by the infused kidney at a high rate, were formed in this organ from the infused catecholamines and were excreted by tubular secretion. Thus, in mammals tubular secretion is linked to an inactivation of these compounds by O-methylation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 4 (1965), S. 507-513 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Mäusen wurde radioaktives DOPA — DL-DOPA-[α-14C], DL-DOPA-[β-T], DL-DOPA-[6-T], DL-DOPA-[2,5,6-T3] — i.p. injiziert. Nach 2 Tagen wurden die Nebennieren entnommen. Zu diesem Zeitpunkt enthalten die Nebennieren Radioaktivität nur noch in Form von Adrenalin und Noradrenalin. Je Tier wurde eine Nebenniere fixiert, während die andere gefriergetrocknet wurde und als Kontrolle diente. Fixationslösung waren 5%iges K2Cr2O7, Orthsche Lösung und Formalin-Calciumchlorid. Nach der Fixation wurden die Nebennieren in Paraffin eingebettet. Die Radioaktivität der Nebennieren wurde im TriCarb gemessen. Die 14C-Aktivität der Catecholamine wird durch bichromathaltige Lösungen zu 60–80% im Gewebe fixiert. Nach Fixation in Formalin-Calciumchlorid enthalten die Nebennieren dagegen nur noch etwa 10% der Aktivität der unbehandelten Kontrollen. Tritiummarkierte Catecholamine verlieren durch Fixation und Paraffin-Einbettung einen größeren Prozentsatz an Radioaktivität als 14C-markierte Catecholamine. Die Tritium-Verluste variieren dabei je nach dem Sitz der 3H-Markierung und der angewandten Fixation. Die Tritium-Markierung der Seitenkette war am beständigsten.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: Dopamine ; Secretion ; Adrenal Medulla ; Catecholamine ; Biosynthesis-Rate ; Dopamin ; Sekretion ; Nebennierenmark ; Catecholamine ; Biosyntheserate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cats and rabbits were injected intravenously with3H-tyrosine and the radioactivity of the catecholamines in adrenal glands and adrenal blood was measured up to 60 min after injection. Adrenal blood was collected in a cava pocket. In addition the specific activity of free3H-tyrosine in blood plasma was measured as a function of time. Radioactive dopamine could be demonstrated in venous blood from adrenals of cat and rabbit by different methods (column chromatography with Dowex 50, paper chromatography, high voltage paper electrophoresis). On the other hand arterial blood flowing to the adrenals contained no3H-dopamine. During the 30 min after the injection of3H-tyrosine cat adrenals secreted about 14% of the synthesized radioactive catecholamines as3H-dopamine and 8% as3H-noradrenaline. In contrast to this the adrenals of rabbits secreted not more than 3% as3H-dopamine and about 20% as3H-noradrenaline. The catecholamine biosynthesis rate of the adrenals and their dopamine resting secretion was estimated from the specific activity of3H-tyrosine in blood plasma and the radioactivity of catecholamines in adrenal glands and adrenal blood. In cats two adrenals synthesized 0.75 mμMol/min catecholamine per kg body weight and in rabbits 0.074 mμMol/min/kg body wt. respectively. The dopamine resting secretion in cats was about 0.08 mμMol/min and in rabbits about 0.002 mμMol/min.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 283 (1974), S. 107-114 
    ISSN: 1432-1912
    Keywords: Kidney ; Adrenaline ; Catechol-O-methyltransferase (COMT) ; Inhibition ; H22/54 [(±)-α-Dihydroxyphenyl]-n-valeramid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the dog kidney catecholamines are O-methylated before being secreted by the tubule (Hempel et al., 1973). Adrenaline was used in an investigation to determine whether or not O-methylation is a prerequisite for the tubular secretion of a catecholamine in the dog. In dogs (n=3) treated with the COMT inhibitor H22/54 [(±)-α-(3,4-dihydroxyphenyl)-n-valeramid] the excretion of 14C-(±)-adrenaline and the pattern 14C-adrenaline metabolites in urine were measured. 14C-adrenaline (9.2 μg per injection) was injected simultaneously with 3H-inulin into both renal arteries. Eigth injections of radioactive material were given to each animal. COMT was inhibited before the second 14C-adrenaline injection by infusion of H22/54 into the left renal artery in doses of 0.16, 0.72 and 3.2 mg/kg b.w., respectively. Without H22/54 the injected dose of 14C-adrenaline was excreted by the kidney within 12 min as followed: 22.2 ± 6.0% (n=6) as 14C-adrenaline, 21.8 ± 7.0% (n=7) as 14C-metanephrine, and 9.3 ± 2.2% (n=7) as deaminated or conjugated 14C-adrenaline metabolites. H22/54 reduced the excretion of 14C-metanephrine to 9–28.2% of the control value, whereas the 14C-adrenaline excretion was considerably increased, up to 200% of the control. It is concluded that the additional 14C-adrenaline observed in urine after COMT inhibition was secreted by the tubule. Thus, O-methylation seems not to be a prerequisite for tubular secretion of adrenaline in the dog.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 295 (1976), S. 123-126 
    ISSN: 1432-1912
    Keywords: Dopamine ; Kidney ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 14C-Dopamine at a dose between 0.16 and 400 nmol per kg body weight was injected locally into the renal artery and urinary excretion of the label was followed for a period of up to 75 min. During the first renal passage the injected kidney excreted 28.2±8.3% (n=8) of the activity applied. As shown by column chromatography the 14C-activity in urine was mainly present as 3,4-dihydroxyphenyl acetic acid (40%), homovanillic acid (15%) and dopamine (app. 20%). Excretion rate and the pattern of dopamine metabolites in urine was independent of the administered dose. Thus, the excretion of dopamine by the cat kidney is linked to an inactivation by the kidney enzymes MAO and COMT. From the literature it is known that in dog and chicken kidney catecholamines are not metabolized to such a large extent during renal excretion.
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  • 7
    ISSN: 1432-1912
    Keywords: Dopa formation ; Tyrosine hydroxylase ; Dopa decarboxylase ; Adrenal gland ; Cat ; Dopa-Bildung ; Tyrosin-Hydroxylase ; Dopa-Decarboxylase ; Nebenniere ; Katze
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach Injektion von H-3-Tyrosin wurde die Bildung von H-3-Dopa in verschiedenen Organen (Nebenniere, Hirnstamm, Herz, Leber, Niere, Milz, Pankreas und Blut) des Huhnes und der Katze gemessen. Die Isolierung von H-3-Dopa wurde wie folgt durchgeführt: 1. Die säurelösliche Fraktion wurde durch Papierhochspannungselektrophorese im Pyridin-Eisessig-Puffer vorgetrennt. 2. Die Tyrosin-Dopa-Bande wurde eluiert und papierchromatographisch aufgetrennt. 3. Die Dopa-Bande wurde erneut eluiert und Dopa wurde als Borat-Komplex durch Papierhochspannungselektrophorese in einem Borat-Puffer charakterisiert. Nach Hemmung der Dopa-Decarboxylase mit NSD-1034 [N-Methyl-N-(3-hydroxybenzyl)hydrazin-dihydrogenphosphat] betrug der Anteil des H-3-Dopa an der Gesamtaktivität der säurelöslichen Fraktion der Nebenniere beim Huhn 4% und bei der Katze 5%. Unter diesen Bedingungen konnte H-3-Dopa in allen anderen untersuchten Organen nicht nachgewiesen werden. Ohne NSD-1034 fand sich auch in der Nebenniere kein H-3-Dopa. Bei Versuchen an Katzen wurde die H-3-Dopa-Konzentration im venösen Blut der Nebenniere gemessen. In einigen Blutproben betrug die H-3-Dopa-Aktivität bis zu 3% der Gesamtaktivität. Nahezu die gesamte von der Nebenniere gebildete Menge an H-3-Dopa wurde an das venöse Blut abgegeben. Nur 5% des neugebildeten Dopa waren am Ende des Versuches in der Nebenniere nachweisbar. Das zeigt, daß Dopa von der Nebenniere nicht gespeichert wird. Im Blut anderer Organe fand sich hingegen kein Dopa. Die Dopa-Konzentration der Nebenniere betrug nach Blockierung der Dopa-Decarboxylase ca. 1 μg/g Naßgewebe und war ohne Hemmung 〈0,2 μg/g. Die Dopa-Neubildungsrate der Nebenniere wurde abgeschätzt aus dem H-3-Dopa-Gehalt der Nebenniere sowie aus dem zeitlichen Verlauf der H-3-Dopa-Aktivität und der spezifischen Aktivität des freien H-3-Tyrosins. Bei der Katze werden von einer einzelnen Nebenniere etwa $$\frac{{0,02{{\mu}}g}}{{\min /kg}}$$ Dopa gebildet $$\left( { = \frac{{1,2{{m\mu Mol}}}}{{\min /1{{gNebenniere}}}}} \right)$$ .
    Notes: Summary After injection of H-3-tyrosine the synthesis of H-3-dopa was measured in various organs (adrenal glands, brain stem, heart, liver, kidney, spleen, pancreas and blood) of fowl and cat. The isolation of H-3-dopa was carried out in the following way: 1. The acid soluble fraction was fractionated by high voltage paper electrophoresis in a pyridine-acetic acid-buffer. 2. The tyrosine-dopa-spot was eluated and descending paper chromatography was carried out. This system separated tyrosine from dopa. 3. The dopa-spot was eluated again, and dopa was characterized by its complex with boric acid in paper high voltage electrophoresis in a boric acid-sodium hydroxide-buffer. After inhibition of the dopa decarboxylase by NSD-1034 [N-methyl-N-(3-hydroxybenzyl)hydrazine dihydrogen phosphate] H-3-dopa represented in adrenal glands of domestic fowl 4% and in those of cats 5% of the total radioactivity. Under these conditions in all the other organs investigated H-3-dopa could not be detected. Without NSD-1034 H-3-dopa was undetectable in the adrenals, too. In experiments with cats the H-3-dopa concentration in the venous blood of the adrenals was measured. In some samples H-3-dopa represented up to 3% of the total radioactivity. Nearly the total amount of H-3-dopa formed in the adrenals was secreted into the venous blood, and only 5% of the total amount were detected in the gland at the end of the experiments. This demonstrates that dopa cannot be stored by the adrenals. We failed to detect H-3-dopa in blood from any other organ. The concentration of dopa in the adrenals was about 1 μg/g wet weight after inhibition of dopa decarboxylase and without inhibition it was 〈0.2 μg/g wet weight. The dopa synthesis rate in adrenals was calculated from the H-3-dopa activity in the gland and in the venous blood and from the specific activity of its precursor H-3-tyrosine. One adrenal of the cat synthetized 0.02 μg dopa/min·kg body weight (=1.2 mμMol/min·1 g adrenal).
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 266 (1970), S. 50-60 
    ISSN: 1432-1912
    Keywords: DOPA-Pool ; DOPA Decarboxylase ; Adrenal Gland ; Catecholamines ; DOPA-pool ; DOPA Decarboxylase ; Nebenniere ; Katecholamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 3H-tyrosine was administered to cats as a continuous i.v. infusion of 30 min duration after inhibition of DOPA-decarboxylase by N-methyl-N′(3-hydroxybenzyl) hydrazine dihydrogen phosphate (= NSD-1034). Subsequently, the content of3H-DOPA in the arterial blood, adrenal glands and adrenal venous blood was measured. For this purpose DOPA was separated from tyrosine and other radioactive tyrosine catabolites by ion exchange chromatography after adsorption onto and elution from alumina. 3H-DOPA was not only detectable in the adrenal glands and in the adrenal venous blood but also in the arterial blood. The content of DOPA in the arterial blood increased linearly during the 30 min infusion period and was 0.5 mμmole/ml at the end of the experiment. This corresponds to a DOPA content in the total blood volume of about 27.5 mμmole/kg body weight. Both adrenals synthesized 0.3 mμmole DOPA per minute and per kg body weight. The significance of the formation of a DOPA pool for the therapeutic use of DOPA decarboxylase inhibitors is discussed.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 265-276 
    ISSN: 1432-1912
    Keywords: Erythrocytes ; Catechol-O-Methyl Transferase (COMT) ; Catccholamines ; Isoproterenol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Washed human red cells, suspended in an isotonic electrolyte solution, were incubated with radioactive catecholamines (epinephrine, norepinephrine, dopamine and isoproterenol). Their conversion to 3-O-methyl derivatives was demonstrated by ion exchange chromatography for each substrate. There was no O-methylation if the erythrocytes were boiled or hemolyzed prior to incubation or if the catechol-O-methyl transferase (COMT) inhibitor pyrogallol was added to the incubation medium. Only catecholamines were methylated by this system, as could be demonstrated by using the non-catecholamine orciprenaline as substrate. Experiments with l-methionine-(methyl-14C) showed that the methylation was brought about by the transfer of a methyl group from l-methionine to the 3-hydroxy group of epinephrine. Thus, this enzymatic system had the properties of COMT. Our experiments therefore suggest that COMT is present in human erythrocytes.
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  • 10
    ISSN: 1432-2013
    Keywords: Renal Handling ; Nɛ-Monomethyl-l-Lysine ; Nɛ-Dimethyl-Lysine ; Nɛ-Trimethyl-Lysine ; Sperber Technique ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The renal handling and the metabolism of3H-labeled Nɛ-methylatedl-lysines1 were investigated in dogs. In one dog the endogenous clearance of some basic amino acids including methyllysines was measured. In the chicken kidney a possible tubular secretion of TML was checked using the Sperber technique. The following results were obtained: 1. l-MML is reabsorbed in the kidney similar to lysine. 2. l-DML has a smaller renal reabsorption than lysine. 3. The clearance ofl-TML is in the range of the inulin clearance. No evidence for tubular secretion ofl-TML has been obtained. 4. Forl-TML the lowest metabolism of all three methylated lysines has been found. The different behaviour of methyllysines in the kidney is discussed with respect to their different physico-chemical properties.
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