EFFECT OF DRUGS ON UPTAKE OF NORADRENALINE BY ISOLATED HYPOTHALAMIC VESICLES

Noradrenaline storing vesicles were isolated from the pig hypothalamus by differential centrifugation, suspended in histidine-HCl buffer and incubated with reserpine, prenylamine or desmethylimipramine. Reserpine and prenylamine (each 6 × 10-5 M) inhibited the ATP-Mg++-dependent uptake of noradrenaline by the vesicles as well as the Ca++ and Mg++ stimulated ATPase. Desmethylimipramine (0.6-60 × 10-8 M) blocked the uptake of catecholamine without influencing the ATPase activity. The inhibitory effect of desmethylimipramine was dependent on the concentration of noradrenaline. It is concluded that reserpine and prenylamine inhibit the active uptake of noradrenaline by affecting the ATPase activity whereas desmethylimipramine competitively replaces noradrenaline from the sites of the vesicles which are responsible for the uptake and thereby blocks the influx of noradrenaline. © 1969.