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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 631-640 
    ISSN: 1432-1912
    Keywords: Carrier-mediated outward transport ; Noradrenaline ; Model analysis ; Veratridine ; Vesicular trapping after reserpine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to simulate the outward transport of 3H-noradrenaline induced by veratridine from adrenergic varicosities, a mathematical two-compartment model was developed in which the two compartments (representing axoplasm and storage vesicles) are arranged in series. Simulated results were compared with experimental results obtained with 100 μmol/l veratridine + 1 mmol/l ouabain and rat vasa deferentia kept in calcium-free solution (Bönisch and Trendelenburg 1987). As in experiments, the time course of efflux of 3H-noradrenaline had a pronounced and early peak under RPU-conditions, a minor peak under PU-conditions, and solely a plateau under U-conditions (where R stands for pretreatment with reserpine, P for pretreatment with pargyline, and U for inhibition of COMT by U-0521). From the width of the peak of release, it was deduced that — under RPU-conditions — about 40% of neuronal 3H-noradrenaline are distributed into the axoplasm, about 60% into the storage vesicle. However, this estimate represents an average value; the results are compatible with the view that the ratio “axoplasmic/vesicular 3H-noradrenaline” is quite variable from rat to rat. Under U-conditions, calculations confirm that reserpinelike compounds induce an efflux of tritium that consists predominantly of deaminated 3H-metabolites. The stimulation of outward transport, on the other hand, causes an efflux of tritium that consists predominantly of 3H-noradrenaline; indeed, the efflux of deaminated 3H-metabolites declines (as it did in experiments). Simulations showed further that the highest rates of outward transport of 3H-noradrenaline were achieved when there was a simultaneous induction of outward transport of 3H-noradrenaline and a reserpine-like effect (as it is known to occur when tissues are exposed to veratridine; Bönisch and Trendelenburg 1987). While there was satisfactory agreement between simulated and experimental results under various conditions, there were also two discrepancies that may be caused by a) inhomogeneous labelling of the storage vesicles in individual varicosities (RPU 〈 PU 〈 U) and b) saturation of outward transport of 3H-noradrenaline when a reserpine-like compound greatly increases the axoplasmic level of total noradrenaline (under U-conditions).
    Type of Medium: Electronic Resource
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