Neurogenic secretion of catecholamines from the adrenal medulla in rabbits, induced by administration of insulin, caused decreases in both the dopamine-beta-hydroxylase activity and the catecholamine content of the storage vesicle fraction. After sedimentation through a sucrose density gradient, the storage vesicles obtained from insulin-treated animals had the same density and the same ratio of dopamine-beta-hydroxylase to catecholamine as did vesicles from untreated animals. These and other data indicate that neurogenic secretion from the adrenal medulla occurs by an all-or-none release from the storage vesicles.
The uptake of 3H-labeled imipramine ([3H]IMI) in rat carpus striatum slices was found to be strongly temperature-dependent. The accumulation was shown to be saturable and two apparent Km's were found: 2.2 x 10(-8) and 3.5 x 10(-7) M. Once incorporated, the labeled drug was released from superfused slices by K+ (55 mM) depolarization in the presence of calcium ions. Imipramine was also studied for its ability to induce the release of [3H]dopamine ([2H]DA) which had been previously accumulated by striatal slices. It was found that striatal slices superfused during 1 or 6 min with imipramine (10(-6) - 10(-4) M) release substantial amounts of radioactive dopamine, independently of the presence of Ca2+ in the medium. This release is completely abolished after reserpine pretreatment. It is proposed that imipramine enters the dopaminergic storage vesicles and displaces dopamine. An intraneuronal mechanism of action for imipramine is discussed.
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