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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 393-396 
    ISSN: 1432-1912
    Keywords: Isoprenaline ; Uptake2 ; Extracellular potassium ; Rat heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The kinetics of the inhibitory effect of extracellular K+ on uptake2 of3H-(±)-isoprenaline were determined in isolated hearts obtained from reserpine-pretreated rats; catechol-O-methyl transferase was inhibited. 1. Initial rates of uptake2 of a very low concentration of3H-(±)-isoprenaline (10 nmol/l) were determined in the presence of various extracellular concentrations of K+ (2.7 to 60 mmol/l). The inhibitory effect of K+ was concentration-dependent with an IC50 of about 20 mmol/l. — In these experiments KCl was added to the perfusion solution, and some hypertonicity resulted. In some experiments NaCl was added to a solution containing 5 mmol/l K+ to result in the same degree of hypertonicity as that obtained for 60 mmol/l K+; hypertonicity increased the initial rate of uptake2 of3H-(±)-isoprenaline. Thus, the inhibitory effect of K+ had been slightly underestimated. 2. In subsequent experiments the increase of the concentration of K+ in the perfusion fluid to 30 mmol/l was compensated for by a corresponding reduction of Na+. Initial rates of uptake2 of 10 nmol/l3H-(±)-isoprenaline were determined in the absence and presence of various concentrations of unlabelled (±)-isoprenaline. At 30 mmol/l K+ the IC50 (=K m for uptake2) did not significantly differ from that determined in an earlier study of 2.7 mmol/l K+ (Grohmann and Trendelenburg 1984). Finally, theV max for uptake2 of3H-(±)-isoprenaline was determined at either 2.7 or 30 mmol/l K+. At 30 mmol/l K+ theV max was only about 1/4 of that observed at 2.7 mmol/l K+. 3. Extracellular K+ inhibits uptake2 of3H-(±)-isoprenaline primarily by a reduction ofV max.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Neuronal deamination ; Extraneuronal deamination ; Rat vas deferens ; Rat heart ; Monoamine oxidase ; Pargyline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two different “deaminating systems” were compared (i.e., intact tissues in which an uptake process translocates the 3H-catecholamine from the extracellular space to the intracellular MAO): 1) the adrenergic nerve endings of the rat vas deferens exposed to 10 nmol/l 3H-(−)-noradrenaline, and 2) the extraneuronal deaminating system of the rat heart perfused with 50 nmol/l 3H-(−)-adrenaline. Vesicular uptake and COMT were inhibited. In both systems MAO was partially inhibited by pargyline, and the steady-state tissue content of the 3H-catecholamine was determined as well as the steady-state rate of deamination. 1. Rat vas deferens (preincubated with 10–40 nmol/l pargyline for 30 min). Inhibition of neuronal MAO caused not more than a moderate decrease of the steady-state rate of deamination of 3H-(−)-noradrenaline, but the steady-state tissue content was greatly increased. Determinations of the activity of MAO in homogenates of vasa deferentia showed that preincubation with 10 and 20 nmol/l pargyline inhibited the enzyme by 80 to 95%. 2. Rat heart (of animals pretreated with 1 to 30 mg/kg pargyline). Inhibition of extraneuronal MAO caused a steep decline of the steady-state rate of deamination of 3H-(−)-noradrenaline but only a small rise in the steady-state tissue content. 3. The decisive difference between the two deaminating systems lies in the fact that the ratio “k mao/k out” (where the two k-values characterize the activity of the unsaturated intracellular MAO and the ability of the 3H-catecholamine to leave the relevant cells, respectively) is much higher for the neuronal deaminating system exposed to 3H-(−)-noradrenaline than for the extraneuronal deaminating system exposed to 3H-(−)-adrenaline. Whenever this ratio is high, pronounced (but incomplete) inhibition of MAO results in a very pronounced increase in the intracellular steady-state 3H-amine concentration (during exposure of the tissue to a 3H-catecholamine); as far as the steady-state rate of deamination is concerned, the pronounced rise in substrate concentration largely masks the pronounced degree of inhibition of MAO. When, however, the ratio is close to unity, inhibition of MAO fails to result in any pronounced increase in the intracellular steady-state 3H-amine concentration; as a consequence, any pronoumced inhibition of MAO is then reflected by a pronounced decrease of the steady-state rate of deamination. 4. From the present results it is concluded that, in experiments with intact tissues, the degree of inhibition of MAO cannot be derived from measurements of rates of deamination of 3H-catecholamines.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: drug surveillance ; adverse drug reactions ; psychotropic drugs ; comparison of assessment methods ; inter-rater agreement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Within an ongoing drug surveillance project (AMÜP) in psychiatric hospitals, a comparative study was carried out to evaluate two methods commonly used in the field of adverse drug reaction assessment. Two raters, who have cooperated with the project since its inception, evaluated 80 randomly selected ADRs twice; first, by an empirical (implicit) approach, and second, 4 weeks later, by using an algorithm as proposed by Kramer et al. 1979. Agreement on medication and related probability ratings was obtained in 81% of all 80 cases for the empirical method (weighted Kappa=0.41), and in 69% for the algorithmic method (weighted Kappa=0.62), indicating that agreement exceeded chance for both methods. By comparison with assessments made in previous case conferences of the project, empirical ratings were found to be reliable over time due to homogeneous use of criteria by project raters. In contrast to the reports on the subject, agreement between raters appeared to be superior in the empirical method as compared to the algorithmic assessment. Analysis of disagreements suggested that probability ratings based on the empirical method were nonspecific, due to conventional criteria applied in the project. Inter-rater agreement was reduced by polypharmacy, especially in the case of algorithmic assessments. The consistency of assessment was also lowered by the fact that the 2 methods assigned different weights to particular assessment criteria.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 332 (1986), S. 34-42 
    ISSN: 1432-1912
    Keywords: Neuronal deamination ; Extraneuronal deamination ; Isotope effects ; 3H-catecholamides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neuronal and extraneuronal disposition of3H-7,8-and3H-7-labelled (−)-noradrenaline and dopamine was compared in in vitro studies. 1. In agreement with earlier studies, the present results show that the presence of a tritium label in position 8 (i.e., on the alpha-carbon) has two consequences: a) the rate of deamination declines and b) part of the deamination results in the formation of an unlabelled aldehyde plus tritium water; tritium water is recovered from the OMDA-fraction of the column chromatographic procedure of Graefe et al. (1973). 2. Whenever the deamination of a3H-catecholamine is reduced (by tritium in position 8), the intraneuronal3H-catecholamine concentration is increased. This increase, in turn, partly masks the decline in neuronal deamination (rat vas deferens). Irrespective of whether one dertermines the spontaneous efflux, the release of3H-noradrenaline by nerve stimulation or the release of3H-(−)-noradrenaline by the reserpine-like compound Ro 4-1284, the presence of tritium in position 8 distorts the results (experiments with rat vasa deferentia and/or rabbit aorta). 3. In the extraneuronal system of the rat heart, two intracellular enzymes inactivate3H-(−)-noradrenaline and3H-dopamine: catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). Any hindrance of deamination (by tritium in position 8, COMT intact) leads to a shift of the metabolism of the3H-catecholamines from the exclusively deaminated to the exclusively O-methylated metabolites. 4. No differences between3H-7,8-and3H-7-labelled catecholamines were found after inhibition of MAO and COMT (extraneuronal accumulation and rate constant for efflux from the extraneuronal compartment III of the rat heart). 5. These results indicate that the presence of tritium in position 8 of catecholamines introduces errors, if monoamine oxidase is active. This is important for the interpretation of earlier results, since virtually all samples of “3H-(−)-noradrenaline” and “3H-dopamine nominally labelled in position 7” were contaminated with varying amounts of tritium in position 8. 6. In some experiments, also3H-7-(−)-adrenaline was used. For adrenergic nerve endings, the rate of metabolism (deamination) declined in the order:3H-7-dopamine 〉 3H-7-(−)-noradrenaline 〉 3H-7-(−)-adrenaline. For the extraneuronal disposition the ranking order was:3H-7-(−)-adrenaline 〉 3H-7-(−)-noradrenaline=3H-7-dopamine. However, in the extraneuronal disposition of3H-(−)-adrenaline, O-methylation predominated over deamination.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Biotechnology letters 8 (1986), S. 1-6 
    ISSN: 1573-6776
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A promoterles DNA fragment containing theE. coli xylose isomerase gene and its ribosome binding site was ligated into a plasmid downstream from the strong λ PL promoter. The plasmid was then used to transformE. coli strains containing a temperature-sensitive λ repressor (cI857). The transformants overproduced xylose isomerase when the repressor was thermally inactivated.
    Type of Medium: Electronic Resource
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