Bibliothek

X
feed icon rss

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
Filter
  • Efflux of noradrenaline metabolites  (2)
  • Rabbit heart  (2)
  • 1
    Digitale Medien
    Digitale Medien
    The influence of the rate of perfusion on the kinetics of neuronal uptake in the rabbit isolated heart (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 275-283 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Rate of perfusion ; Neuronal uptake ; Accessibility of neuronal uptake sites ; Perfusion pressure ; Rabbit heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Rabbit hearts (with monoamine oxidase and catechol-O-methyl transferase inhibited) were obtained from reserpine-pretreated animals. They were perfused at rates ranging from 1.3–11.3 ml·g−1·min−1 with 0.1 mM 14C-sorbitol and various concentrations of 3H-(−)noradrenaline (NA). From measurements of the arterio-venous concentration difference of 3H and 14C activity the removal of NA and sorbitol from the perfusion fluid was followed for 2–3 min at intervals of 5 s. The uptake of NA into intracellular spaces of the heart (known to be over-whelmingly into sympathetic nerve terminals) was obtained by subtracting the removal of sorbitol from that of NA. If was cumulated and plotted against time. 2. The progress curves of NA uptake were sigmoid in shape: following a lag period, uptake proceeded at first at a constant initial rate and from then on at gradually decreasing rates. Irrespective of the NA concentration used, the lag period became shorter and the initial rate of uptake increased whenever the rate of perfusion was increased. Furthermore, at high rates of perfusion the initial rate was maintained for a shorter time than at low ones. 3. At any given perfusion rate, the initial rates of NA uptake obeyed Michaelis-Menten kinetics. While changes of the rate of flow did not alter the apparent K m (range: 2.2–2.4 μM), a rectangular hyperbolic relationship was found between V max and the perfusion rate. The V max was half-maximal at a rate of flow of 2.7 ml·g−1·min−1 and approached a maximum value of 9.0 nmoles·g−1·min−1. 4. From the lack of change in the K m it can be concluded that the uptake sites of the perfused heart are functionally arranged in parallel. The change in V max, on the other hand, indicate that the accessibility of the sites is limited by the rate of perfusion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00508296
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 2
    Digitale Medien
    Digitale Medien
    Saturation kinetics of the adrenergic neurone uptake system in the perfused rabbit heart. A new method for determination of initial rates of amine uptake (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 263-273 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Neuronal uptake ; Initial rates of amine uptake ; Lag period for amine uptake ; Cocaine ; Rabbit heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Hearts were obtained from normal or reserpine-pretreated rabbits and perfused at a constant rate (3.6 ml·g−1·min−1) with Tyrode's solution containing 14C- or 3H-sorbitol and various concentrations of 3H-(−)noradrenaline (NA), 14C-(+)NA or 3H-(±)metaraminol; when NA was used, monoamine oxidase and catechol-O-methyl transferase were inhibited. During perfusion for 2 min the arterio-venous difference for 3H and 14C activity (and in this way the removal of amine and sorbitol from the perfusion fluid) was determined at intervals of 5 s. The uptake of amine into intracellular spaces of the heart was obtained by subtraction of the removal of sorbitol from that of amine; it was cumulatively added and plotted against time (uptake curve). Uptake was overwhelmingly neuronal. 2. The uptake curves were sigmoidal: after a brief initial lag period, uptake curves became linear; there-after, the slope of the curves decreased. The last phase of divergence from linearity occurred the earlier and was the more pronounced, the higher the amine concentration. It was interpreted to indicate that neuronal efflux of amine then began to reduce net uptake. 3. From the slope of the linear phase of the uptake curves initial rates of amine transport were obtained. They were saturable with increasing amine concentrations and obeyed Michaelis-Menten kinetics. The apparent K m values of the three amines were similar in magnitude and ranged from 2.9 to 5.9 μM. Uptake was stereoselective in that the V max of (+)NA was significantly lower than that of (−)NA. Pretreatment with reserpine affected neither the K m nor the V max for uptake. Cocaine was a potent competitive inhibitor of amine transport (K i=0.5–1.0 μM). 4. The intercept of the linear phase of the uptake curves on the time axis (t lag) (corrected for the time necessary for transit through the dead space) was taken as a measure of the lag period. It declined when uptake was progressively saturated (or inhibited) by increasing substrate (or cocaine) concentrations. Moreover, t lag was always linearly correlated with the fraction of amine removed from the perfusion fluid. These findings indicate that the equilibration of the uptake sites with the substrate concentration in the perfusion fluid is delayed by the uptake process itself, especially under low saturation conditions (i.e., when S〈K m).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00508295
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 3
    Digitale Medien
    Digitale Medien
    The disposition of 3H-(−)noradrenaline in the Perfused cat and rabbit heart (1981)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 318 (1981), S. 71-82 
    Details
    ISSN: 1432-1912
    Schlagwort(e): (−)Noradrenaline ; Neuronal metabolism ; Extraneuronal metabolism ; Perfused heart ; Efflux of noradrenaline metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Hearts of cats and rabbits were perfused at a constant rate with 3H-(−)noradrenaline for 60–120 min. During the perfusion the rate of net removal of 3H-noradrenaline from the perfusion fluid and the rate of efflux of 3H-metabolites from the hearts were followed. From these results and from the amount of 3H-metabolites recovered from the hearts (at the end of experiments), the time course of the cumulative metabolite formation was obtained. The following metabolites were determined: 3,4-dihydroxyphenylethyleneglycol (DOPEG), 3,4-dihydroxymandelic acid (DOMA), normetanephrine (NMN) and a fraction consisting of 3-methoxy-4-hydroxyphenylethyleneglycol and 3-methoxy-4-hydroxymandelic acid (OMDA). 2. In normal hearts, the rate of formation of DOPEG, DOMA and OMDA became constant only after a considerable delay, and the rate of efflux of these metabolites did not reach a constant value within 120 min. By contrast, the formation of NMN proceeded at a constant rate throughout the perfusion with 3H-noradrenaline, and the rate of efflux of NMN approached a steady level within about 30 min. 3. In hearts of reserpine-pretreated animals not only NMN, but also DOPEG, DOMA and OMDA quickly approached a constant rate of formation. In addition, the efflux of all metabolites attained a steady level, and after about 70 min, the hearts of both species reached a steady state in which the net removal of 3H-noradrenaline was fully accounted for by the formation of metabolites. 4. The metabolite pattern during the steady state showed striking species differences. The rate of metabolite formation (expressed in % of the steady-state rate of 3H-noradrenaline removal) decreased in the order DOPEG (40.0%)〉NMN (30.8%)〉DOMA (18.1%)〉OMDA (9.0%) in the cat heart and DOPEG (66.8%)〉DOMA (20.0%)〉OMDA (6.6%)〉NMN (1.5%) in the rabbit. 5. In both species, 30 μmol · l−1 cocaine (to inhibit neuronal uptake) decreased the rate of formation of DOPEG, DOMA and OMDA to very low values, but increased the formation of 3H-NMN. 6. In the cat heart, 30 μmol · l−1 hydrocortisone (to inhibit extraneuronal uptake) decreased the formation of NMN, while having no effect on the formation of DOPEG, DOMA and OMDA. Moreover, in the cat and rabbit heart perfused in the presence of cocaine, inhibition of extraneuronal uptake markedly affected the formation of NMN. 7. A linear relationship was found for all metabolites between the rate of efflux and the tissue content (both parameters being determined during steady state), indicating first-order kinetics of efflux. The ranking order of the overall rate constants for efflux was DOPEG≫NMN〉DOMA.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00508829
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 4
    Digitale Medien
    Digitale Medien
    The rate constants for the efflux of the metabolites of noradrenaline from rabbit aortic strips (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 207-215 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Rate constants for efflux ; Efflux of noradrenaline metabolites ; Rabbit aorta ; Metabolism of noradrenaline
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. Rabbit aortic strips were incubated with 1.18 μM labelled noradrenaline for 30 min and then washed with amine-free solution for at least 110 min. From the last efflux sample and from the metabolite content of the strip analysed at the end of the experiment, rate constants for the efflux of the metabolites were calculated in two ways: a) as k = rate of efflux/metabolite content of strip, or b) as the slope of the regression line relating rate of efflux to metabolite content of the strip. Both determinations yielded essentially the same ranking order, and the results of b) indicated that there was no tight binding of metabolites in the tissue. 2. The rate constants for the efflux of glycols (DOPEG and MOPEG) and normetanephrine were much higher than those of the acid metabolites (DOMA and VMA). Although this ranking order agrees with results obtained with perfused hearts, k-values obtained from experiments with incubated strips tended to be lower (by a factor of 1.6 to 14.1) than k-values derived from experiments with perfused hearts. Since this difference was smallest for the acid metabolites and highest for the glycols, it is likely that considerable redistribution of the metabolites with high rate constants takes place in incubated, but less so in perfused tissues. 3. The rate constants for the efflux of metabolites also influence the rate of the approach of the metabolite content of the strip to steady state (during the incubation with noradrenaline): the rate of approach to steady state increases with increasing rate constant for efflux. 4. The apparent half time for the efflux of a metabolite (obtained from the slope of the efflux curve) equals the half time calculated from the rate constant for efflux $$\left( {t/2 = \frac{{1{\text{n 2}}}}{k}} \right)$$ , provided there is no formation of the metabolite during the relevant period of wash out. However, a discrepancy between the two parameters becomes the more noticeable, the higher the rate of formation of the metabolite during the period of observation. 5. In conjunction with earlier observations, the present results show that the efflux of metabolites observed during wash out of tissues previously loaded with noradrenaline is determined by a) the rate constant for efflux (k) and b) the formation (or lack of formation) of the metabolites during the period of observation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00517987
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...