[Choline synthesis in neurons].
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Biomedical subjects
Publications and source records attributed to J C Louis.
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Two kinetic mechanisms are responsible for the uptake of choline in Rat brain synaptosomal fractions with different affinity towards the substrate (high affinity mechanism: Km 5.1 microM, Vmax 44 pmol/mg prot/min.; low affinity mechanism: 35.7 microM, Vmax 286 pmol/mg prot/min). The treatment of synaptosomal fractions with neuraminidase (15 min. at 37 degrees C) followed by 1 min. incubation with various concentrations of [14C] choline reduces the uptake in parallel with the disappearance of the high affinity mechanism (Km 202.2 microM, Vmax 119 pmol/mg prot/min.), without influencing the synthesis of acetylcholine.
The acquisition of ultrastructural and neurochemical properties was studied during the development of neurones from 8-day-old chick embryo cerebral hemispheres, cultivated on polylysine-coated surfaces. The first contacts suggestive of synaptic profiles were observed after 3 days of culture. From the 6th day, junctions with significant thickening of the postsynaptic element and many presynaptic vesicles could be seen. Synaptic endings contained predominantly dense-cored vesicles. These cultured neurones acquired dopaminergic properties during their development: (1) 95% of the cells exhibited glyoxylic acid-induced fluorescence; (2) tyrosine hydroxylase and dopa decarboxylase activities were present and increased with time in culture, but dopamine-beta-hydroxylase activity was undetectable. Choline acetyltransferase activity remained at a very low level at all stages of culture. It is suggested that when cultured in the total absence of glial cells, the neurones of embryonic chick cerebral hemispheres give no evidence of cholinergic mechanisms, but display a number of dopaminergic characteristics.
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We have studied the fatty acid composition of total phosphoglycerides from various types of nerve cells in culture. Primary cell cultures were compared with tumoral cell strains. Glial cells exhibited no characteristic pattern when compared to neurons. Tumoral cell phosphoglycerides contained much higher levels of octadecenoic acid and lower levels of C-20 to C-22 polyunsaturated fatty acids than normal cell phosphoglycerides. This observation seems to be a general feature in tumoral cell membranes. It could be of interest in respect to the membrane fluidity of cancer cells.
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Superoxide dismutase (EC 1.15.1.1) activity was investigated in several types of neural cells cultivated in the presence of 100 mM ethanol. Superoxide dismutase was inhibited by acute treatment with ethanol. Chronic treatment with ethanol specifically inhibited superoxide dismutase in glial cells. In all instances withdrawal of ethanol produced a quick return to control values. Inhibition of superoxide dismutase by ethanol may increase toxic oxygen radicals in nervous tissue.
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In the Dog, 3-(2-hydroxy-3 isopropylamino-proxy)-2-phenyl-1-isoindolinone (RS, SR) possesses an anti-arrhythmic activity similar to that of quinidine but at dose levels 2 to 6 times lower than in the case of the latter compound. Furthermore, in contrast to quinidine, at the dose levels where the antiarrhythmic activity is well observed, the compound is devoid of hypotensive activity and of depressive action on cardiac contractility. The first clinical studies of this compound have shown its usefulness in the treatment of ventricular and supraventricular arrhythmias.
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A stereospecific saturable high affinity binding of 3H-naloxone has been found in 3 glial and 2 neuronal cell lines. Kinetic study of binding seems to indicate only one class of receptor sites in the 5 cell lines. Acute exposure to morphine (1 X 10(-5)M) concurrent with PGE1-induced stimulation of adenylate cyclase did not result in a decrease of the cAMP level in any cell line tested.