Influence of alpha-adrenergic blocking agents on cyclic AMP, cyclic GMP and lipolysis in hamster white fat cells.
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Biomedical subjects
Publications and source records attributed to Y Giudicelli.
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The authors report two cases of lipomatosis. Biochemical study of lipomas revealed, in comparison with normal adipose tissue:--an increase in lipasic lipoprotein activity;--a decrease in lipasic triglyceride activity. These changes could be in part implicated in the mechanisms of fatty accumulation within the lipomas, without explaining the topography and encapsulation.
The effects of glucose and of various inhibitors of glycolysis or of oxidative phosphorylation on stimulated lipolysis and on intracellular cyclic AMP and ATP levels were investigated in isolated human fat cells. The glycolysis inhibitors, NaF and monoiodoacetate, inhibited epinephrine or theophylline-stimulated lipolysis and parallely reduced the intracellular cyclic AMP and ATP levels; however, neither NaF nor monoidoacetate significantly affected dibutyryl cyclic AMP-induced lipolysis. Removal of glucose from the medium also reduced the rate of epinephrine-stimulated lipolysis and the intracellular cyclic AMP and ATP levels but failed to modify the lipolytic activity of dibutyryl cyclic AMP. The oxidative phosphorylation inhibitors, antimycin A and, under fixed conditions, 2,4-dinitrophenol also strongly decreased the adipocyte cyclic AMP and ATP levels but inhibited as well the rate of epinephrine- and of dibutyryl cyclic AMP-induced lipolysis. N-Ethylmaleimide, a mixed glycolysis and oxidative phosphorylation inhibitor, not only reduced the intracellular cyclic AMP and ATP levels and epinephrine- or theophylline-induced lipolysis, but also that stimulated by dibutyryl cyclic AMP. When glycolysis was almost fully inhibited, human fat cells were insensitive to epinephrine but remained fully responsive to dibutyryl cyclic AMP. These results, showing a relationship between ATP availability, cyclic AMP synthesis and lipolysis, suggest a different ATP requirement for cyclic AMP synthesis and triacylglycerol lipase activation, a difference which could explain why ATP issued from glucose breakdown appears to be a determinant factor for cyclic AMP synthesis, but not for triacylglycerol lipase activation in human fat cells.
2-Mercaptoethanol-induced fatty liver involves an increased free fatty acid mobilization which is primarily due to an inhibition of free fatty acid reesterification in adipose tissue. Furthermore, increased free fatty acid mobilization as well as fatty liver induction are not induced by 2-mercaptoethanol per se but result most probably from 2-mercaptoacetate through oxidation of 2-mercaptoethanol.
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A case of severe lead poisoning with haemolytic anemia, extensive polyneuropathy and arterial hypertension is reported in a patient for whom G-6-P-D deficiency and renal tubular acidosis were discovered. Both traits were present in his family. Incomplete regression of paralysis and persistant biological abnormalities after chelating treatment were demonstrative of heavy saturnine load even though the toxic exposure was brief. The role of the two deficiencies in the mechanism of intoxication is discussed: facilitation of haemolysis by enzymopathy and bone lead redistribution resulting from osteolysis probably due to the tubulopathy. The authors emphasize the fact that thorough and serial biological investigation is essential in the discovery of factors which may precipitate lead poisoning, as well as in the determination of follow-up criteria of efficient toxic epuration with sufficient delay. Typing of the enzyme has led to the identification of a new variant of glucose-6-phosphate dehydrogenase deficiency.
The effects of some mono-, di- and tricarboxylic substrates (acetate, pyruvate, L-lactate, L-alanine, D,L-beta-hydroxybutyrate, succinate, D,L-malate, alpha-oxoglutarate, L-glutamate and citrate) on the basal lypolytic activity of isolated white adipocytes from fasted rats were investigated "in vitro". At concentrations ranging from 1 to 10 mM, the compounds tested, except lactate, had no influence on the rate of glycerol release but markedly reduced the free fatty acid (FFA) release. Lactate reduced both the glycerol and FFA release. As this "in vitro" lowering effect on FFA release was observed using concentrations occurring "in vivo" in the blood for lactate, beta-hydrobutyrate, and alanine, these results suggest that, besides lactate and beta-hydroxybutyrate, alanine may also assume an important role in the "in vivo" regulation of peripheral FFA mobilization and consequently of ketogenesis.
1. Trypsin-treated human and rat fat cells were obtained by digestion of adipose tissue with collagenase plus trypsin and their lipolytic response to insulin, catecholamines and dibutyryl cyclic AMP were compared with the lipolytic response of human and rat fat cells isolated with collagenase only. 2. In both human and rat fat cells, no significant modification occurred in the intracellular lactate dehydrogenase content and in the basal release of glycerol after trypsination. 3. In rat fat cells, trypsin abolished the antilipolytic effect of insulin but maintained a normal lipolytic response to epinephrine, norepinephrine and isoproterenol. 4. In human fat cells, on the contrary, trypsin failed to modify the antilipolytic effect of insulin, but markedly potentiated the lipolytic response to epinephrine, norepinephrine and isoproterenol. Trypsin also increased the rate of intracellular 3' :5' cyclic AMP accumulation in response to catecholamines. Under these conditions, however, trypsin-treated human fat cells had a normal reponse to the lipolytic agent dibutyryl cyclin AMP. 5. These data suggest that human fat cells differ from the rat ones by the existence in human adipocyte membranes of a trypsin-sensitive component which inhibits the catecholamine induced lipolytic process and which is different from the alpha receptors.
1. This investigation was undertaken for the purpose of determining the structure of the phosphatidylcholines of lung surfactant system present at birth in normal full term newborn infants. 2. The procedure, using tracheal aspirates as lung secretions, combines a cold-acetone precipitation and a two-dimensional thin-layer chromatography of the lipid extract. 3. Different species of phosphatidylcholines were isolated and found to account together for over 60% of the total phospholipids in tracheal aspirates. Analysis of the fatty acids esterifying the alpha- and beta-carbon of these different phosphatidylcholines showed palmitic acid as the major component with little myristic acid. 4. This fatty acid analysis revealed furthermore that the major phosphatidylcholine fraction was almost exclusively alpha, beta-dipalmitoylphosphatidylcholine. 5. This study shows that the procedure described provides a useful and simple method for the extraction, isolation and characterisation of the functional components of lung surfactant in living human newborns.
The intraperitoneal administration of 2-mercaptoethanol or 2-mercaptoacetate (40 muM/100 g body weight) to the rat induces a fatty liver, a marked and early increase of free fatty acids and a decrease of triacylglycerol and phospholipids in the blood. These changes are accompanied by a decrease of the ketone body level and the beta-hydroxybutyrate/acetoacetate ratio in the liver. Under the same experimental conditions, however, administration of 2-mercaptopropionate fails to induce a fatty liver and does not modify the hepatic ketone body level or the blood triacylglycerol and free fatty acid levels. These results led us to conclude that fatty liver induction is not a general feature of foreign thiols, and suggest that increased peripheral fat mobilization as well as decreased hepatic lipoprotein synthesis and/or release are responsible for the 2-mercaptoethanol- and 2-mercaptoacetate-induced fatty liver.
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1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.
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The phospholipids in tracheal aspirates from normal full term newborn infants were studied and compared to the phospholipids present in the corresponding amniotic fluids. The same classes of phospholipids were recovered from both fluids, i.e. lysophosphatidylcholine (LPC), phosphatidylserine (PS), phosphatidylinositol (PI), sphingomyelin (S), phosphatidyldimethylethanolamine (PDME), phosphatidylethanolamine (PE), polyglycerophosphatides (PGP), phosphatidic acids (PA) and two different species of phosphatidylcholine (PC-1 and PC-2). Except for PA, the proportion as well as the fatty acid composition of each of these phospholipids was similar in tracheal aspirates and in amniotic fluids. The predominant fraction (PC-1) was the most saturated one. PI, PDME, LPC and S were, like PC-1, predominantly constituted by saturated fatty acids and accounted together for a concentration equivalent to that of PC-1. Since tracheal aspirate originates from the lung, these data suggest that the pulmonary surfactant activity in normal full term newborn infants results not only from the presence of PC-1, but also from that of PI, PDME, LPC and S.
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1. The oral administration of propan-2-ol [isopropanol; 100 mmol (6 g)/kg body weight] or ethanol [130 mmol (6 g)/kg body weight] to starved rats produced no change in plasma post-heparin lipase activity (PHLA) compared with that observed in 154 mmol/1 sodium chloride (saline)-treated rats. 2. An increase of adipose tissue lipoprotein lipase (LLA) and a decrease of heart LLA occurred in isopropanol-treated animals, whereas no significant changes were found in these activities after ethanol administration. 3. Since administration of isopropanol produces hyperglycaemia, observations were also made in rats receiving glucose infusion rather than saline. In these animals a rise in PHLA and adipose tissue LLA, and a fall in heart LLA, occurred. 4. It is suggested that the changes in tissue LLA produced by isopropanol are mediated by the rise in blood glucose.
Administration of noramidopyrine or of noramidopyrine-methane-sulfonate interferes with the determination of blood uric acid by both the colorimetric method of Folin-Denis and an enzymatic uricase peroxidase method. This interference which is observed at least during the 24 hours following intravenous administration of noramidopyrine, results in either an increase (Folin-Denis) or a decrease (uricase) of the intensity of the final colour. The same effects are also observed in vitro when one adds noramidopyrine to an aqueous solution of uric acid. Existence of this interference should be taken into consideration especially in the diagnosis, the prognosis and the analgesic treatment of renal lithiasis.