�ber den Mechanismus der Catecholamin-Speicherung in den ?chromaffinen Granula? des Nebennierenmarks

Taugner, G.; Hasselbach, Wilhelm

doi:10.1007/bf00541021

Cited by 63 publications

(17 citation statements)

References 25 publications

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“…The present results demonstrate that not only reserpine-like drugs (Taugner & Hasselbach, 1966; but also neuroleptics inhibit the amine uptake by membranes of amine storage organelles. However, the mechanism of action of these two classes of drugs seems to differ from that of false neurotransmitters like octopamine.…”

Section: Discussionsupporting

confidence: 55%

“…The isolated membranes of adrenal chromaffin granules were used as a model system since it has not yet been possible to obtain pure amine storage organelles from the brain. Chromaffin granules are available in a highly purified form, and their membranes have been shown to take up biogenic amines by a specific, probably carriermediated adenosine-5'-triphosphate (ATP)-dependent transport mechanism (Taugner & Hasselbach, 1966;Taugner, 1971;Kirshner, 1974;Da Prada, Obrist & Pletscher, 1975 (Helle, 1971;. Previous …”

Section: Introductionmentioning

confidence: 99%

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Effect of Neuroleptics and Other Drugs on Monoamine Uptake by Membranes of Adrenal Chromaffin Granules

Pletscher

1977

British J Pharmacology

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The effects have been investigated of various reserpine‐like, neuroleptic, antidepressant and other compounds on the adenosine‐5′‐triphosphate (ATP)‐dependent uptake of noradrenaline (NA) (reserpine‐sensitive) and tryptamine (reserpine‐resistant) by membranes of isolated chromaffin granules of bovine adrenal medulla. Reserpine and Ro 4–1284 (2‐hydroxy‐2‐ethyl‐3‐isobutyl‐9,10‐dimethoxy‐hexahydro‐11bH‐benzo(a)quinolizine) as well as neuroleptics (e.g. chlorpromazine and haloperidol) inhibited the NA uptake, but the reserpine‐like drugs were more potent. In contrast, Ro 4–1284 showed a considerably weaker effect than the neuroleptics in interfering with tryptamine uptake. Chlorpromazine had about the same potency in inhibiting NA and tryptamine uptake, whereas the action of haloperidol was more pronounced on the uptake of NA than of tryptamine. The relative potencies of neuroleptic drugs in inhibiting NA uptake by granule membranes in vitro corresponded only partly to their relative potencies in enhancing dopamine turnover in vivo. The inhibition of NA uptake by chlorpromazine and Ro 4–1284 appeared to be of the noncompetitive type. Chlorpromazine did not influence the decrease in ATP induced by granule membranes in the incubation medium. Other basic, but not acidic compounds also inhibited NA uptake by granule membranes; their potency was of the order of that of chlorpromazine (antidepressants) or weaker (e.g. benzodiazepines). In conclusion, the mechanism of action of neuroleptics probably differs from that of reserpine‐like drugs in the inhibition of monoamine uptake by membranes of catecholamine storage organelles. While interference with the granular storage of dopamine at the granule membrane level may contribute to the in vivo action of neuroleptics (e.g. in enhancing dopamine turnover), additional effects of these drugs must be involved in vivo, e.g. blockade of pre‐ and postsynaptic dopamine receptors.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Effect of Neuroleptics and Other Drugs on Monoamine Uptake by Membranes of Adrenal Chromaffin Granules

Pletscher

1977

British J Pharmacology

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“…The mechanism of action of reserpine in inhibiting the amine uptake is also uncertain. In previous experiments, evidence has been presented that reserpine might interfere with a specific transport ATPase located in the adrenal granular membranes (Taugner & Hasselbach, 1966). If this were the case, one would have to postulate that two or more ATPases with different reserpine sensitivity are involved in the transport of the various amines.…”

Section: Degradation Of a Tpmentioning

confidence: 99%

Discrimination of Monoamine Uptake by Membranes of Adrenal Chromaffin Granules

Prada

Obrist

Pletscher

1975

British J Pharmacology

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The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis. Adenosine‐5′‐triphosphate (ATP) in the presence of Mg++ stimulated the uptake of all the amines tested, but the accumulation of dopamine, (‐)‐noradrenaline (NA), 5‐hydroxytryptamine (5‐HT), (±)‐adrenaline and (±)‐octopamine was greater than that of tyramine, (±)‐metaraminol, tryptamine, β‐phenylethy lamine and histamine. At the higher concentration levels of the amines in the medium the ATP‐dependent accumulation of dopamine, NA, adrenaline and 5‐HT in the membranes reached a saturation level, whereas in the absence of the nucleotide no saturation level was attained. Octopamine and 5‐HT competitively inhibited the ATP‐dependent uptake of NA. Decrease in the incubation temperature or the presence of N‐ethylmaleimide greatly reduced the ATP‐stimulated amine accumulation. Ouabain had no effect on uptake. Reserpine virtually abolished the ATP‐dependent uptake of dopamine, NA and 5‐HT, caused a partial inhibition of the metaraminol, octopamine and tyramine accumulation, but did not interfere with the uptake of tryptamine. The content of endogenous catecholamines of the membranes was changed very little by incubation of NA and 5‐HT in the presence of ATP. However, the membranes lost over 80% of their endogenous amines if incubated for 30 min without ATP. The ATP content of the medium progressively decreased during the incubation of granular membranes. It is concluded that the membrane of adrenal chromaffin granules discriminates between the various monoamines with regard to the magnitude of their uptake and that two mechanisms of ATP‐stimulated uptake, one responsive and the other resistant to reserpine, exist at the level of this membrane. The ATP‐stimulated transport at the granular membrane level may be an important factor in determining the intraneuronal storage of a physiological or false neurotransmitter.

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“…The uptake and storage of noradrenaline and other amines by intraneuronal storage vesicles are inhibited not only by reserpine but by a number of other drugs, including prenylamine, desmethylimipramine and other tricyclic antidepressants, tetrabenazine, chlorpromazine and other phenothiazines, haloperidol and other butyrophenones, some indirectly acting sympathomimetic amines, uncouplers of oxidative phosphorylation, metabolic inhibitors, EDTA, some <X-receptor antagonists and some p-receptor antagonists (KIRSHNER, 1962;CARLSSON et aI., 1963b;EULER and LISHAJKO, 1968;TAUGNER and HASSELBACH, 1966;PHILIPPU et aI., 1965PHILIPPU et aI., , 1967PHILIPPU et aI., , 1969BURGER et aI., 1968BURGER et aI., , 1969.…”

Section: Uptake Of Amines By Nerve Vesicles and Adrenal Granulesmentioning

confidence: 97%