Interaction of proteins with aggregates of catecholamines and nucleotides: possible biological implications.
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Biomedical subjects
Publications and source records attributed to A Pletscher.
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1. By density gradient centrifugation of homogenized blood platelets of guinea-pigs, subcellular organelles have been isolated which exhibit much higher concentrations (mumole/mug protein) of ATP than the whole platelets.2. The organelles also store endogenous 5-HT whose concentration is, however, considerably inferior to that of ATP.3. Investigated by electron microscopy most of the isolated organelles look empty and only very few show dense osmiophilic cores indicating the presence of 5-HT. Accordingly the occurrence of dense osmiophilic organelles in the whole platelets is also very rare.4. Exogenous 5-HT taken up by the platelets markedly accumulates in the subcellular fraction containing the organelles storing ATP. Concomitantly, the platelets show a rise in the number of osmiophilic organelles and the frequency of osmiophilic cores in the isolated organelles is increased.5. From these and previous in vitro experiments it is concluded that the so called 5-HT storage organelles of blood platelets primarily store ATP and only subsequently accumulate 5-HT.
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1. After intraperitoneal administration of L-2-(14)C-3-O-methyldopa ((14)C-O-methyldopa) to rats, the amino-acid was distributed evenly in blood, brain, heart, adipose tissue and liver, whereas it accumulated more in the kidney and the pancreas. (14)C-O-methyldopa showed a biological half-life of about 12-13 h in blood, brain and heart.2. The concentration curve of (14)C-O-methyldopa in brain (after increasing doses of the amino-acid) was linear if measured 2 h after administration, but seemed to reach a plateau at the higher doses if determined after 16 h.3. The concentrations of (14)C-O-methyldopa metabolites (mainly homovanillic acid and 4-hydroxy-3-methoxyphenyllactic acid) were low, except in the kidney, and varied according to the tissue.4. Twenty-four hours after administration of (14)C-O-methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main (14)C-homovanillic acid and (14)C-4-hydroxy-3-methoxyphenyllactic acid) and of 5% of unchanged (14)C-O-methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end-products.5. It is concluded that (14)C-O-methyldopa easily penetrates from the blood into various tissues, including brain, and that the majority of the amino-acid undergoes a slow metabolism. The different shape of the concentration curves for (14)C-O-methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino-acid.
1. From aqueous solutions of biogenic amines, such as noradrenaline plus adenosine triphosphate (ATP), a second liquid phase spontaneously separates in the presence of small amounts of bivalent cations such as calcium. This separation is reversible and temperature-dependent; the concentration of amine and ATP in the bottom phase is several times higher than in the supernatant.2. Analytical ultracentrifugation provides evidence that the second phase consists of high molecular weight aggregates of the amine and ATP.3. The separated second phase of the noradrenaline-ATP system dissolves isothermally on addition of tyramine and amphetamine which in vivo are known to liberate biogenic monoamines and which have a low tendency to aggregate with ATP. The apparent molecular weights of noradrenaline-ATP aggregates are decreased by tyramine and amphetamine. Dopamine does not diminish the second phase and it can also form aggregates of high molecular weight with ATP.4. Bivalent cations in high concentrations diminish or abolish the separation of a second phase.5. Small amounts of reserpine affect phase separation.6. It is concluded that the physico-chemical properties of aggregates of biogenic amines with ATP may be of importance for understanding the storage and release of the amines in vivo.
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