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A Pletscher

Publications and source records attributed to A Pletscher.

At least 91 records · Page 5Linked to original sources
PubMed1976

Actin associated with membranes of monoamine storage organelles.

A histo-immunofluorescence technique using anti-actin antibodies has been applied to various subcellular fractions of bovine adrenal medulla and rabbit blood platelets. In the adrenal medulla only the membranes of the chromaffin granules, but not the fractions containing other subcellular particles (microsomes, mitochondria) showed marked immunofluorescence was present in the membranes of the 5-hydroxy-tryptamine organelles as well as in other subcellular particles. It is concluded that in the adrenal medulla, actin is specifically associated with the membranes of the amine storage organelles, whereas in platelets the protein shows a rather general subcellular distribution.

Actins↗
PubMed1976

Transport of monoamines in membranes of adrenal chromaffin granules: physiological and pharmacological aspects.

The membranes of isolated bovine adrenal chromaffin granules take up catecholamines by an ATP-dependent process which fulfills many criteria of a carriermediated energy-requiring transport. This transport together with an intragranular mechanism probably explains the high storage capacity of the chromaffin granules for catecholamines. 5.2 Other amines (e.g. 5-hydroxytryptamine (5HT), octopamine) are also taken up by the membranes, but to a different degree. This probably explains why amines normally not present in storage organelles, if available in increased amounts, may accumulate within these organelles and function as false neurohumoral transmitters. 5.3. Two mechanisms of amine uptake seem to exist at the level of the granule membranes, one reserpine-sensitive (transporting, for instance, catecholamines and 5HT), and one reserpine-resistant (transporting tryptamine and partly metaraminol). Both mechanisms depend on ATP. 5.4. Chlorpromazine interferes with the reserpine-sensitive as well as the reserpine-resistant uptake of noradrenaline (NA) by granule membranes to a similar degree. Consequently the mechanism of action of neuroleptics and reserpine at the granule membrane level are probably different. 5.5. There is only an incomplete parallelism between the inhibition of NA-uptake by granule membranes in vitro and the degree of enhancement of neuronal DA turnover in vivo caused by various neuroleptics. Therefore, factors other than interference with the amine transport through the granule membranes must be co-determinant in the neuroleptic induced enhancement of DA turnover in vivo.

Adrenal Medulla↗
PubMed1975

Lysergic acid diethylamide: evidence for stimulation of cerebral dopamine receptors.

In the rat, lysergic acid diethylamide (LSD) decreased the striatal and retinal content of homovanillic acid. LSD did not change the level of dopamine (DA), but delayed the a-methyl-p-tyrosine-induced disappearance of this amine in the teldiencephalon. In the cat, LSD diminished the DA output into the perfusate of the caudate nucleus. Furthermore, LSD increased the activity of adenylate cyclase in striatal homogenates of rat. These and other findings indicate that in the central nervous system LSD stimulates DA receptors which may be involved in LSD-induced phychosis.

Animals↗
PubMed1975

Interference of inhibitors of dopamine-beta-hydroxylase with uptake of monoamines by chromaffin granular membranes.

Disulfiram and bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA 63) markedly inhibited the Mg2+/ATP-dependent uptake of various monoamines, e.g. dopamine (DA), by isolated membranes of bovine adrenal chromaffin granules. Both compounds affected DA-beta-hydroxylase (DBH) activity more markedly than the uptake of DA. Other inhibitors of DBH, e.g. fusaric acid and diethyldithiocarbaminate (DDC), did not interfere with DA uptake. Disulfiram and FLA 63, in contrast to fusaric acid and DDC, also caused a partial inhibition of Mg2+-dependent ATPase. It is concluded that the inhibition of monoamine uptake by disulfiram and FLA 63 is not related to their effect on DBH.

Adenosine Triphosphatases↗
PubMed1975

Discrimination of monoamine uptake by membranes of adrenal chromaffin granules.

1 The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis. 2 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), (plus or minus)-adrenaline and (plus or minus)-octopamine was greater than that of tyramine, (plus or minus)-metaraminol, tryptamine, beta-phenylethylamine and histamine. 3 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. 4 Octopamine and 5-HT competitively inhibited the ATP-dependent uptake of NA, 5 Decrease in the incubation temperature or the presence of N-ethylameimide greatly reduced the ATP-stimulated amine accumulation. Ouabain had no effect on uptake. 6 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. 7 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. 8 The ATP content of the medium progressively decreased during the incubation of granular membranes. 9 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.

Adenosine Triphosphate↗
PubMed1975

Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency.

Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.

Alkaline Phosphatase↗
PubMed1975

The stereoisomers of 3,4-dihydroxyphenylserine as precursors of norepinephrine.

The action of the four stereoisomers of 3,4-dihydroxyphenylserine (DOPS) on the monoamine content of brain and heart was investigated with biochemical and histochemical methods. The (+)-erythro-DOPS (50-250 mg/kg i.p.), due to its alphaS configuration, was readily decarboxylated in vivo leading to an accumulation of norepinephrine (NE) in brain and heart. The amino probably corresponded to the unnatural (+) form since the amino acid shows betaS configuration. The NE was located in brain regions rich in noradrenergic (hypothalamus, locus ceruleus), dopaminergic (neostriatum, substantia nigra) and 5-hydroxytryptaminergic (raph'e nuclei) neurons. In addition, (+)-erythro-DOPS decreased the level of endogenous 5-hydroxytryptamine and dopamine and increased that of 5-hydroxyindoleacetic and homovanillic acid in the brain indicating a displacement of 5-hydroxytryptamine and dopamine, respectively, from their storage sites. Inhibitors of extracerebral decarboxylase (benserazid and carbidopa) diminished the (+)-erythro-DOPS-induced increase in cerebral NE by inhibiting the decarboxylation of the amino acid in the walls of the brain capillaries. The (-)-threo-DOPS, which also show alphaS configuration, was decarboxylated too, leading to a rise in cardiac NE. The amine was likely to correspond to the natural(-)-isomer since (-)-threo-DOPS has betaR configuration. This increase in NE lasted much longer than that caused by (+)-erythro-DOPS. In the brain, the accumulation of NE was negligible after i.p. administration of (-)-threo-DOPS but marked after injection of the isomer into a cerebral ventricle indicating a poor penetration of (-)-threo-DOPS through the blood-brain barrier. High doses (500 and 1000 mg/kg i.p.) of (-)-erythro- and (+)-threo-DOPS caused only a slight increase in cerebral and cardiac NE since, due to their alphaR configuration, they were probably not decarboxylated to a major extent. In conclusion, (+)-NE formed from (+)-erythro-DOPS probably accumulates in the storage sites of the endogenous monoamines where it might function as a false neurotransmitter.

Animals↗