Regulation of prostaglandin E2 and F alpha productions by rat brown fat during the perinatal period; effects of ambient temperature.
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Biomedical subjects
Publications and source records attributed to R Bertin.
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In this study, we investigated in parallel the evolution of endogenous catecholamine and cyclic nucleotide levels in lung tissue in the course of normal fetal development of the rat from day 17 of gestation to day 10 postpartum; the findings were correlated with the successive stages of lung differentiation. These were assessed morphologically by electron microscopy, and biochemically by measuring the levels of the main lung tissue phospholipids and studying their fatty acid composition. Dopamine levels were low and always remained under 5 ng/g of wet tissue. Nevertheless, slight rises were observed between days 17 and 19 of gestation (1.8 and 2.78 ng/g, respectively) and between days 21 of gestation and birth (2.56 and 4.25 ng/g, respectively). These changes were significant (P less than 0.05). Norepinephrine (NE) levels first decreased by about 50% between days 17 and 19 of gestation (7.34 and 3.88 ng/g, respectively), (P less than 0.01) and then rose sharply about 4 times until birth (17.24 +/- 3.90 ng/g), and more slowly from then on. On day 10 postpartum, the mean NE level was 34.31 +/- 3.28 ng/g. The levels of the two cyclic nucleotides [cyclic adenosine 3':5'-monophosphate and cyclic guanosine 5'-monophosphate (cGMP)] were quite high on day 17 and remained so until day 19 (cAMP = 220 pmoles /g; cGMP = 20 pmoles/g). From day 19 until day 21, the levels of the two nucleotides decreased (cAMP = 140 pmoles/g; cGMP = 8 pmoles/g; P less than 0.05). During this period, the decrease in cGMP level was about twice that of cAMP. During the last day of gestation, the cAMP level was still decreasing, whereas cGMP was increasing. After birth, the levels of the two cyclic nucleotides rapidly increased to day 5. Between days 5 and 10 postpartum, no significant changes were observed in either cAMP or cGMP levels. The time course of the variations reported suggests that they are related to the maturation processes of lung assessed on the basis of morphological and biochemical criteria. On day 19 of gestation, when the first lamellar bodies appear, large changes occur in the evolution of NE and cyclic nucleotide levels, suggesting that these changes may be related to the onset of surfactant synthesis. On day 21 of gestation, the cAMP and cGMP ratio rises sharply; at the same time, the total phospholipid level is increased by 50%. At this stage, lamellar bodies are actively differentiating within type II pneumocytes and massively released into the fetal airways. The relationships between the variations of the studied biochemical parameters and the maturation processes of lung suggest that dopamine and NE could be involved in surfactant synthesis and release via their second messenger, the cyclic nucleotides. Further investigations are needed to elucidate the mechanisms regulating these changes.
The development of adjuvant arthritis induced important modifications in intracellular levels of cyclic AMP and GMP in primary and secondary lymphoid organs: a continuous decrease in cyclic AMP and a biphasic increase in the level of cyclic GMP which correlate well with the onset of the acute phase and the systemization of the disease.
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A new micro-method was used to determine the effects of cold acclimation of rats on the levels of prostaglandin E2 and F alpha in both white and brown adipose tissues. Whereas PGF alpha levels were significantly higher than PGE2 levels in white fat, no difference between the amounts of the two prostaglandins was observed in brown fat. In both tissues, cold acclimation did not induce any change in prostaglandin levels.
The variation in the amounts of cyclic AMP and cyclic GMP were studied in white and brown adipose tissues and in the liver of rats during the first week of cold exposure (5 degrees C). In white fat, only a small increase in cAMP was observed on the first day. In brown fat, parallel decreases in cAMP and cGMP contents were induced which might be related to a large mobilization of tissue fatty acids. In the liver, cold exposure barely affected the cAMP content but the level of cGMP was markedly increased. These results are discussed with regard to the respective role of these different tissues in cold-induced energetic substrate mobilization.
In view to study a possible regulation of lipoprotein lipase (LPL) activity by tissue cyclic nucleotide levels (cAMP and cGMP), parallel determinations of the three factors were performed on brown adipose tissue (BAT), epidymal fat (WAT) and heart of rats. Opposite variations of cAMP levels and LPL activity were only observed in WAT following high fat diet administration. The enhancement of LPL activity in BAT and in heart by cold acclimation or feeding an hyperlipidic diet was never associated with a decrease in cAMP content. The variations of cAMP and cGMP levels were not dependent. It is concluded that there is no effect of cyclic nucleotide levels in the enhancement of LPL activity in these tissues.
The intracellular level of adenosine 3':5'-monophosphate (cyclic AMP) and its stimulation in vitro by norepinephrine were studied in brown and white adipocytes from rats adapted to constant or fluctuating cold. Cold acclimatization had no effect on the basal cyclic AMP intracellular content in both tissues, but the level in brown adipocytes was four-fold higher than in the white ones. Addition of norepinephrine in the incubation medium doubled the cyclic AMP content of white adipocytes from control or fluctuating-cold-adapted rats, and enhanced four-fold in constant-cold-adapted rats. In brown adipocytes norepinephrine increased cyclic AMP levels in the first two groups, but had no effects in constant-cold-adapted rats. In the two tissues of control and fluctuating-cold-adapted rats the norepinephrine action was increased by phentolamine and decreased by propranolol. The lack of response to norepinephrine of brown adipocytes from constant cold-adapted rats was not due to the predominance of the alpha component of hormone receptors. Antilipolytic drugs (nicotinic acid, insulin and prostaglandin E2) inhibited the action of norepinephrine on white adipocytes; only prostaglandin E2 had an effect on brown ones.
Glycerol release by brown adipocytes from constant cold adapted rats was not stimulated by norepinephrine. On the contrary, the release was stimulated in rats adapted to a nycthemeral fluctuatiing temperature from 5 degrees to 28 degrees C. Glycerokinase activity was greatly increased in brown adipose tissue by cold adptation ; there was no change in the liver. However this increased activity cannot entirely explain the lack of norepinephrine stimulation of glycerol release in the brown adipose tissue of cold adapted rats.
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3':5'-Cyclic-AMP phosphodiesterase (PDE) (EC 3.1.4.17) activity was measured in interscapular brown adipose tissue (BAT) and in white epididymal adipose tissue of rats acclimated to constant or fluctuating cold. Experiments were carried out on isolated adipocytes or tissue homogenates. In brown or white adipose tissue or isolated adipocyte homogenates, two different apparent Km values were found according to the substrate (cAMP) concentration. The low Km was at about 10(-6) M and the high one at about 10(-4) M. The apparent V of the high Km enzyme was about 10-fold higher than the V of the low Km enzyme. Cold acclimation to constant or fluctuating cold did not modify appreciably the Km or V values. For low substrate concentrations (10(-6)-10(-8) M), the specific activity of PDE expressed per milligram of protein was decreased in BAT adipocytes of the two groups of cold-acclimated rats, compared to controls. Inversely, it was increased in total tissue homogenates. These variations were smaller in fluctuating cold than in constant cold-acclimate rats. They could, in part, induce the increases in lipolysis and in blood flow observed in the BAT of cold-acclimated rats.
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