ISSN:
1432-1912
Keywords:
Chromaffin granule ghosts
;
PC-12 cells
;
Rat vas deferens
;
Dobutamine
;
Uptake1
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Possible effects of (±)-dobutamine on adrenergic nerve endings were determined in experiments with ghosts of bovine chromaffin granules, with rat phaeochromocytoma (PC-12) cells and with the rat vas deferens. Dobutamine inhibited the vesicular uptake of a mixture of 70% adrenaline + 30% 3H-noradrenaline into ghosts, with an IC50 of 1.7 μmol/l. Dobutamine inhibited uptake, of 3H-noradrenaline in PC-12 cells (with an IC50 of 0.38 μmol/l) without being a substrate. However, dobutamine easily entered PC-12 cells by diffusion. After inhibition of MAO, COMT and vesicular uptake dobutamine (15 and 45 μmol/l) released tritium from rat vasa deferentia preloaded with 3H-noradrenaline. Equi-inhibitory concentrations of dobutamine and desipramine (against uptake1) were equireleasing. On the other hand, when MAO and vesicular uptake were intact, dobutamine (15 μmol/l) increased the efflux of tritium from preloaded vasa deferentia much more than did an equi-inhibitory concentration of desipramine. Most of the released tritium was then 3H-DOPEG. Dobutamine is a potent inhibitor of uptake1 as well as of vesicular uptake; moreover, it easily diffuses into adrenergic nerve endings. Hence, it blocks the neuronal and the vesicular re-uptake of noradrenaline; consequently, when MAO and vesicular uptake are intact, dobutamine increases the net leakage of noradrenaline from the storage vesicles, thereby leading to an efflux of deaminated metabolites. However, dobutamine is virtually unable to release noradrenaline into the extracellular space.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00165130
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