Adrenergic False Transmitters

Muscholl, E.

doi:10.1007/978-3-642-65249-3_14

Cited by 20 publications

(9 citation statements)

References 113 publications

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“…of noradrenergic and 5-hydroxytryptaminergic neurones, are able to take up and accumulate amines other than those which they contain under physiological conditions. For instance, in the central nervous system L-DOPA causes an accumulation of dopamine not only in dopaminergic but also in 5-hydroxytryptaminergic neurones (Bartholini, Da Ng, Chase, Colburn & Kopin, 1970), and a-methyl-dopa leads to an increase of ct-methyl-dopamine and a-methyl-noradrenaline in catecholaminergic neurones (Muscholl, 1972).…”

Section: Introductionmentioning

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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Section: Introductionmentioning

confidence: 99%

Discrimination of Monoamine Uptake by Membranes of Adrenal Chromaffin Granules

Prada

Obrist

Pletscher

1975

British J Pharmacology

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“…Metaraminol is taken up by a process which is not stimulated by ATPMg2+, not inhibited by reserpine, and which, although possibly carrier mediated, saturates only at extremely high substrate concentrations (53). The physiological relevance of this second type uptake is unclear (52), but it is o f consid erable pharmacological importance in permit ting 'false transmitters' (such as metaraminol) to enter the vesicles and exert their pharmaco logical effects (37). Additionally, measurement o f the uptake o f metaraminol relative to that of catecholamines is o f value in utilization of uptake as a tool in physiological and pharmaco logical studies (vide infra).…”

Section: Is Vesicular Catecholamine Uptake Actually a Transport Process?mentioning

confidence: 99%

“…The transport site in the vesicle mem brane is thus far more primitive in its selectivity than its uptake!, and is also less specific than the intravesicular storage complex (55). The greater selectivity o f the storage site within the synaptic vesicle compared to the transport site would appear to play a greater role than does vesicular transport in determining which amines can remain within the vesicle to act as catechol amine displacers or false transmitters (37,55).…”

Section: Characteristics Of the Vesicular Transport Sitementioning

confidence: 99%

Uptake of Catecholamines by Storage Vesicles

Slotkin¹,

Bareis²

1980

Pharmacology

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“…We have no direct evidence why adrenaline should be the least affected of the hypothalamic catecholamines after chronic a-methyldopa treatment, but this result was certainly not due to methodological problems associated with the radioenzymatic assay, since the methoxy derivative of adrenaline was always fully separated from those of all other catecholamines on paper chromatography. There has been some speculation whether a-methyladrenaline is formed in nervous tissue (Muscholl, 1972). Although a-methyladrenaline has been reported to be present in appreciable amounts only in tissues with high PNMT activity (e.g., adrenal gland; Muscholl, 1972), and hypothalamic PNMT activity is only about 2% of that found in the adrenal, the amine could still be found in trace, but important, amounts.…”

Section: Discussionmentioning

confidence: 94%

“…There has been some speculation whether a-methyladrenaline is formed in nervous tissue (Muscholl, 1972). Although a-methyladrenaline has been reported to be present in appreciable amounts only in tissues with high PNMT activity (e.g., adrenal gland; Muscholl, 1972), and hypothalamic PNMT activity is only about 2% of that found in the adrenal, the amine could still be found in trace, but important, amounts. In fact further investigations have indicated that in vitro a-methylnoradrenaline is a substrate for hypothalamic PNMT (P. M. Beart & W. J. Louis, unpublished observations) and thus a-methyladrenaline could be formed in the brain if a-methylnoradrenaline is available to PNMT.…”

Section: Discussionmentioning

confidence: 94%

Adrenaline Depletion in the Hypothalamus of the Rat After Chronic Α‐methyldopa

Beart

Prosser

Louis

1981

Clin Exp Pharma Physio

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1. Individual anterior hypothalamic-preoptic nuclei were dissected from the brains of control and alpha-methyldopa treated (2 x 40 mg/kg, 5 days) rats, and the concentrations of adrenaline and other catecholamines were estimated. 2. By a combination of radioenzymatic assay and paper chromatography the concentrations of adrenaline, noradrenaline, dopamine, alpha-methylnoradrenaline and alpha-methyldopamine were determined concurrently in the same sample. 3. alpha-Methyldopa reduced the adrenaline levels of the hypothalamic nuclei by 47--68% of control concentrations. 4. A differential displacement of the parent catecholamines was observed and the depletions were ranked: adrenaline less than dopamine less than noradrenaline. 5. alpha-Methylnoradrenaline and alpha-methyldopamine were found in all hypothalamic nuclei. 6. The depletion of hypothalamic adrenaline by alpha-methyldopa could represent a pharmacological mechanism contributing to the antihypertensive action of the drug.

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Adrenergic False Transmitters

Cited by 20 publications

References 113 publications

Discrimination of Monoamine Uptake by Membranes of Adrenal Chromaffin Granules

Discrimination of Monoamine Uptake by Membranes of Adrenal Chromaffin Granules

Uptake of Catecholamines by Storage Vesicles

Adrenaline Depletion in the Hypothalamus of the Rat After Chronic Α‐methyldopa

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