Abstract
Human neuroblastoma cells of sympathetic origin have been used for studying the effects of diosmin and its metabolite diosmetin (vasotonic agent) on amine reuptake systems. Neuroblastoma cells take up 3H-dopamine in a specific and time-dependent manner. 3H-dopamine uptake was dose-dependently inhibited by the known antagonist desipramine. Diosmin did not affect 3H-dopamine uptake at concentrations as high as I m m. On the other hand the aglycone metabolite of diosmin, diosmetin, inhibited 3H-dopamine uptake in a dose-dependent manner (IC50=4 μm). Diosmetin inhibited 3H-dopamine uptake in control and differentiated neuroblastoma cells, as well as in small-cell lung carcinoma cells. Furthermore diosmetin also inhibited 'H-serotonin uptake in both cell types. These results demonstrate that some flavonoids act as antagonists of plasmamembrane amine transporters at the molecular level and suggest that inhibition of amine reuptake at the level of peripheral sympathetic nerve terminals could be responsible for the increased vascular tone observed in vivo after treatment with these drugs.
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