Clearance of orally administered115mCd from rat tissues

Summary Peak^115mCd levels in the liver, kidneys, spleen and duodenum of the rat, following a single oral dose, fell exponentially. Half-clearance time for^115mCd is highest in the kidney (30 days) followed by the liver (6.8 days), the spleen (5.5 days) and the duodenum (3.5 days).     

Effect of mycotoxin (T-2 toxin) on catecholamine and Na+, K+-ATPase levels in rat epididymis

Summary The effect of mycotoxin (T-2 toxin) on catecholamines and Na⁺, K⁺-ATPase activities in rat epididymis has been evaluated. Dopamine and norepinephrine levels were significantly elevated in the caput and corpus regions whereas their levels remained unchanged in the caudal part of the epididymis. Na⁺, K⁺-ATPase activity was significantly increased in all the three regions of rat epididymis as a result of the toxin treatment. These changes may suggest an adverse effect on epididymal functions in rats.     

Moderate cooling depresses the accumulation and the release of newly synthesized catecholamines in isolated canine saphenous veins

Summary Moderate cooling (from 37° to 24°C) depressed the formation of³H-dopamine and³H-norepinephrine from³H-tyrosine by isolated canine saphenous veins. Cooling reduced the evoked release ofnewly synthesized catecholamine to the same extent as tha of stored norepinephrine. Hence the augmentation by cold of the contractile response to sympathetic nerve stimulation observed in earlier work is not accompanied by an augmentated release of newly synthesized norepinephrine.Acknowledgments. This work was supported by grant HL 05883 from the National Institutes of Health. The authors want to thank F. Jordaens for his valuable technical assistance, J. Beckman for secretarial assistance and H. Hedrickson for preparing the illustrations.Recipient of training grant 80304 from the I.W.O.N.L.     

Action,in vitro et in vivo,de l'angiotensine II sur le captage cardiaque de la noradrénaline

Summary The action of angiotensin II on cardiac uptake of norepinephrine was investigated in the rat in vivo and in vitro. In contrast to desipramine, neither infusion of subpressive (10 ng/kg/min) or pressive (50–150 ng/kg/min) amounts of angiotensin on intact and/or binephrectomized rats, nor incubation of cardiac slices with angiotensin II (10^–5; 10^–9 M) impair the accumulation of tritiated norepinephrine and the level of metabolites. It is thus concluded that there is no inhibiting action of angiotensin II on the cardiac uptake of norepinephrine.     

α1-Adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

Summary The effect of norepinephrine on fatty acid synthesis (³H₂O incorporation into fatty acids), on fatty acid oxidation to CO₂ and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 M), lipogenesis was lower (5.7±1.1 nmoles³H₂O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5±1.7; n=6, p<0.02). In contrast, (1-¹⁴C) palmitate conversion into total ketone bodies was increased to 10.9±1.8 nmoles/mg/30 min with norepinephrine, vs 8.5±1.6 in controls (p<0.05), and more (1-¹⁴C) palmitate was converted to¹⁴CO₂ with norepinephrine than in controls (1.48±0.10 nmoles/mg/30 min vs 1.06±0.11, p<0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the ₁-receptor blocker prazosin, but not by ₂ or -blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Corticotropin and nonshivering thermogenesis.

Chronic treatment with corticotropin led to reduced calorigenic effect of norepinephrine in cold acclimatized rats, but potentiated its effect in controls. This inhibitory effect was not due to the observed decrease in corticosterone plasma level, as it was shown by metopirone administration. It is concluded that corticotropin could have a competitive action on receptor sites mediating the calorigenic effect of norepinephrine in nonshivering thermogenesis.     

Increased ALA dehydratase activity and spleen weight in lead-intoxicated rats. A consequence of increased blood cell destruction

Summary Lead was given in the diet (1%) to rats from birth and at different times the animals were studied for delta amino levulinic acid dehydratase (ALAD) activity, spleen weight,⁵⁹Fe incorporation in erythrocytes and⁵¹Cr-labeled erythrocytes survival. The increased ALAD and spleen weight found after lead treatment is explained as a consequence of a shortened survival, which results in a younger age of circulating erythrocytes with higher ALAD activity.Supported by Contract No. 140-76-12 ENV. B. of the E. C. Environmental Research Program.     

Corticotropin and nonshivering thermogenesis

Summary Chronic treatment with corticotropin led to reduced calorigenic effect of norepinephrine in cold acclimatized rats, but potentiated its effect in controls. This inhibitory effect was not due to the observed decrease in corticosterone plasma level, as it was shown by metopirone administration. It is concluded that corticotropin could have a competitive action on receptor sites mediating the calorigenic effect of norepinephrine in nonshivering thermogenesis.Grateful acknowledgment is expressed to Mrs M. Lopez for her technical assistance.     

Comparison of the biological effects of anemia inducing and polycythemia inducing Friend virus complex

Summary The comparison of the biological effects of FV^P and FV^A showed that leukemogenesis appears to be delayed in FV^A infected mice as compared to FV^P infected animals after injection of comparable quantities of virus as measured in spleen focus forming units. In addition, no CFU-EI, characteristic for FV^P induced leukemia, were found in leukemic spleen or bone marrow of FV^A infected mice. Since it was possible to distinguish both viruses by their different host ranges, which are helper virus determined, it is suggested that the observed differences, especially the lack of CFU-EI in FV^A infected mice, might be due to differences in the helper virus component of the FV complex.Supported by the Deutsche Forschungsgemeinschaft (SFB 112 Zellsystemphysiologie).     

Growth hormone alters lymphocyte sub-populations and antibody production in dwarf rats in vivo

Female dwarf rats at different ages were treated with recombinant porcine GH or with a potent sheep anti-rat GH serum. Body weight and spleen weight increased with GH and decreased with anti-GH treatment (p<0.001). Neither GH nor anti-GH treatment resulted in a change in circulating WBCs, but GH decreased, while anti-GH increased, RBC counts (p<0.001). Similarly, GH treatment tended to decrease the ratio of CD4⁺:CD8⁺ T-cells while anti-GH increased (p<0.05) the ratio. Anti-GH treatment also enhanced the animals' ability to produce specific IgG in response to KLH injection. These results indicate that GH may have a physiological role in suppressing humoral immune function but may enhance cell-mediated immunity.     

Mitogenicity of autolysates ofTrypanosoma congolense

Summary Autolysates ofTrypanosoma congolense, in subcytotoxic amounts, were found to be highly mitogenic in vitro for the spleen cells of normal mice. Significant amounts of [³H]-thymidine were also incorporated by the responding spleen cells of nu/nu (athymic) mice. In contrast, the spleen cells of cyclophosphamide-treated mice were unresponsive. The findings suggest that a potent B-cell-mitogen is generated by the autolysingT. congolense organism.Acknowledgments. This investigation was supported by the International Development Research Centre, Canada.     

Aging of the erythrocyte. III. Cation content

Summary Studies on the main cation content of density-separated bovine erythrocytes showed a progressive decrease in the levels of K⁺ and Mg²⁺ with increasing cell density (and age) accompanied by an increase in the level of Na⁺. The magnitude of net cation loss corresponded to that of red cell volume decrease, but could not account for the total increase in the microviscosity of the erythrocyte interior.     

β-Adrenergic stimulation of androgen production by fetal mouse Leydig cells in primary culture

Summary The responsiveness of fetal mouse Leydig cells to catecholamines (epinephrine, norepinephrine), a-agonist agent (L-isoproterenol) and hCG was investigated in vitro. Fetal Leydig cells when freshly isolated were unable to respond to L-isoproterenol (10^–5M). However, L-isoproterenol, epinephrine and norepinephrine significantly stimulated androgen production by fetal Leydig cells after 24 h of primary culture. Androgen production was increased in both conditions and to a greater extent by hCG. Propranolol blocked the stimulatory effect of L-isoproterenol and epinephrine. It is concluded that catecholamines can regulate fetal testosterone biosynthesis.     

Intracellular NAD(H) levels control motility and invasion of glioma cells

Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD⁺ and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD⁺-salvage, accompanies the changes in NAD(H) during tumorigenesis. Here, we show by genetic and pharmacological inhibition of NAMPT in glioma cells that fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease. Extracellular supplementation of NAD⁺ or re-expression of NAMPT abolished the effects. The effects of NAD(H) decrease on cell motility appeared parallel coupled with diminished pyruvate-lactate conversion by lactate dehydrogenase (LDH) and with changes in intracellular and extracellular pH. The addition of lactic acid rescued and knockdown of LDH-A replicated the effects of [NAD(H)] on motility. Combined, our observations demonstrate that [NAD(H)] is an important metabolic component of cancer cell motility. Nutrient or drug-mediated modulation of NAD(H) levels may therefore represent a new option for blocking the invasive behavior of tumors.     

Effect of acute and chronic ethanol ingestion on the content of reduced glutathione of various tissues of the rat

Summary The effect of acute ethanol ingestion (5 g/kg) by fasted rats, or chronic treatment in fed animals, revealed a significant decrease in the content of reduced glutathione of the liver and kidney. No changes were observed in reduced glutathione levels of the pancreas, intestines, stomach or spleen in the acute model. In this condition, the time course study of the decrease in reduced glutathione levels showed a progressive effect in the liver and a rapid and constant effect in the kidney.These studies were supported by the Grant M 308-792 from the Servicio de Desarrollo Cientifico, Artistico y de Cooperacion Internacional, Universidad de Chile, and by the Research Associateship Program (L.A.V.) from the Natural Sciences and Engineering Research Council of Canada.     

The accumulation pattern of ingested gossypol in selected organs of the rat.

Bound gossypol levels in the spleen and kidney of rats ingesting dietary gossypol (0.98%) varied directly with the feeding intervals of 6, 14, 28 and 35 days. Free gossypol level in the kidney, spleen and lungs increased for 14 days and then tended to decrease as the feeding period was extended.     

Heart norepinephrine concentration after chronic alcohol ingestion in the rat

Summary The effect of long-term alcohol ingestion on the norepinephrine concentration of the heart was investigated in rats. The alcoholic animals showed a highly significant increase in cardiac norepinephrine concentration as compared with the corresponding controls. It is further suggested that continued exposure to high levels of norepinephrine may play a role in the development of cardiomyopathy in chronic alcoholism.     

The accumulation pattern of ingested gossypol in selected organs of the rat

Summary Bound gossypol levels in the spleen and kidney of rats ingesting dietary gossypol (0.98%) varied directly with the feeding intervals of 6,14, 28 and 35 days. Free gossypol level in the kidney, spleen and lungs increased for 14 days and then tended to decrease as the feeding period was extended.     

Taux de renouvellement de la noradrénaline dans le canal déférent et la vésicule séminale du Rat

Summary The turnover times and the synthesis rates of tissue norepinephrine were determined in the vas deferens and in the seminal vesicle of the rat from the rate of disappearance of H³-norepinephrine after an i.v. injection ofl-H³-norepinephrine. The labelled amine disappeared from the two organs by a single exponential decline thus behaving kinetically as though it was stored in a single pool.     

Kinetics of BRCA1 regulation in response to UVC radiation

To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to increasing doses of ultraviolet C. We observed an increase in BRCA1 protein levels above 78 J/m². This increase was observed as early as 5 min after irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent with the previously published data. By pretreating with cycloheximide prior to irradiation, we observed a decrease in the protein half-life, from 3.5 h to 53 min, suggesting that a decrease in protein half-life may cause the lower levels of BRCA1 after irradiation. We also observed an increase in BRCA1 mRNA within 15 min of irradiation, followed by a decrease after 4 h. These data suggest that newly translated protein may contribute to increases in BRCA1 protein levels. The very rapid changes in BRCA1 support its role as a sensor of DNA damage, as opposed to being a repair gene. Received 6 April 2000; received after revision 23 May 2000; accepted 23 May 2000