Der Einfluss von 2-Deoxy-D-glucose auf die Substratoxydation in Ascites-Tumorzellen

Summary The effect of the glycolytic inhibitor 2-deoxy-D-glucose on the oxidation of¹⁴C-labelled substrates of the tricarboxylic acid cycle was investigated in ascites carcinoma cells of the mouse. In the presence of high concentrations of glucose, deoxyglucose stimulates the oxidation of pyruvate C-2 and C-3 to CO₂, but not the oxidation of succinate C-1,4 to CO₂. While deoxyglucose causes, in the absence of glucose, an inhibition of the oxidation of exogenous palmitate C-1 to CO₂, it causes, in the presence of glucose, a stimulation of the palmitate oxidation. There is a possible correlation between the effect of deoxyglucose on the intracellular ATP metabolism and the effect of deoxyglucose on the palmitate oxidation.     

Über die Wirkung blutzuckersenkender Sulfonylharnstoffe auf das isolierte Rattenzwerchfell

Summary The action of blood sugar depressing sulfonylureas on glucose and oxygen uptake, as well as on glycogen content and formation of C¹⁴O₂ from uniformly labelled C¹⁴-glucose was investigated in rat hemidiaphragms incubated in phosphate buffer. The following results were obtained: (1) Tolbutamide and Carbutamide increased the glucose uptake. (2) Tolbutamide decreased the glycogen-content. (3) Oxygen uptake as well as formation of C¹⁴O₂ were increased by Tolbutamide. (4) The action of Tolbutamide and insuline was equal with respect to glucose uptake but different as regarding the glycogen content, oxygen uptake and CO₂-formation.It is concluded that sulfonylureas increase glucose oxidation in the rat hemidiaphragm probably without increasing insulin sensitivity. To our knowledge this mechanism of action has hitherto not been described.     

Dual modes of 5-(N-ethyl-N-isopropyl)amiloride modulation of apical dipeptide uptake in the human small intestinal epithelial cell line Caco-2

Selective pharmacological Na⁺/H⁺ exchange (NHE) inhibitors were used to identify functional NHE isoforms in human small intestinal enterocytes (Caco-2) and to distinguish between direct and indirect effects on transport via the intestinal di/tripeptide transporter hPepT1. The relative potencies of these inhibitors to inhibit ²²Na⁺ influx identifies NHE3 and NHE1 as the apical and basolateral NHE isoforms. The Na⁺-dependent (NHE3-sensitive) component of apical dipeptide ([¹⁴C] Gly-Sar) uptake was inhibited by the selective NHE inhibitors with the same order of potency observed for inhibition of apical ²²Na⁺ uptake. However, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) also reduced [¹⁴C]Gly-Sar uptake in the absence of Na⁺ and this inhibition was concentration and pH (maximal at pH 5.5) dependent. NHE3 inhibition by S1611 and S3226 modulates dipeptide uptake indirectly by reducing the transapical driving force (H⁺ electrochemical gradient). EIPA (at 100 μM) has similar effects, but at higher concentrations (>200 μM) also has direct inhibitory effects on hPepT1.Received 28 February 2005; received after revision 20 April 2005; accepted 20 May 2005     

The distribution of carcinogens, 4-nitroquinoline-1-oxide and 4-hydroxyaminoquinoline-1-oxide,in the nervous system and its possible neurotoxicological significance

Summary 4-NQO-¹⁴C can enter the grey matter parenchyma of the central nervous system of mice after i.v. injection. The level of its uptake by the central grey is higher than that taken up by the central white and by the trigeminal and spinal dorsal root ganglia. This pattern of distribution is strikingly different from that obtained after i.v. injection of 4-HAQO-¹⁴C, suggesting the possible occurrence of 4-NQO encephalomyelopathy having entirely different sites of lesions from those of 4-HAQO neuropathy.This work was supported by a grant-in-Aid for Special Project Research from the Ministry of Education, Science and Culture of the Japanese Government (No. 321304, 1978).     

Transient ischemic alteration of synaptosomal neutral acid uptake

Summary The effect of cerebral ischemia and postischemia on the synaptosomal uptake of some neutral amino acids was determined in mongolian gerbils at various periods of time. A transiently increased uptake of³H isoleucine,¹⁴C cycloleucine and³H phenylalanine in the synaptosomes was found after 3 min of bilateral common carotid occlusion which returned to normal at 30 min of reestablished cerebral blood circulation.     

The effect of insulin on the glycogen metabolism of isolated fat cells

Résumé (1) Des adipocytes isolés à partir du tissu adipeux épididymaire du rat ont été incubés dans des milieux contenant du glucose (1¹⁴C) et des concentrations variables d'insuline. La quantité de glucose (1¹⁴C) transformée en glycogène (¹⁴C), (¹⁴C)O₂ et triglycerides (¹⁴C) a été déterminée. (2) On démontre que la quantité de glucose (1¹⁴C) transformée en glycogène par des adipocytes peut être évaluée et qu'elle est fonction de la concentration d'insuline. (3) La comparaison entre les effets d'insuline sur les transformations du glucose (1¹⁴C) en glycogène (¹⁴C), en triglycerides (¹⁴C) ou (¹⁴C)O₂ révèle que l'insuline a une action apparemment directe sur l'incorporation du glucose au glycogène. (4) Ce fait serait donc dû à un effet direct de l'insuline sur une réaction dans la synthèse du glycogène par les adipocytes ou à une grande affinité des enzymes participant à la synthèse du glycogène pour le glucose-1-phosphate et à leur faible capacité pour la synthèse du glycogène.     

Uptake of glucose-C14 and fructose-C14 by buffalo spermatozoa in extenders during cold storage

Summary Buffalo spermatozoa exhibit insignificant uptake of glucose-C¹⁴ and fructose-C¹⁴ when semen samples were preserved in cold for 96 h in 2 extenders. Incorporation of C¹⁴ in spermatozoa, TCA precipitable proteins and soluble sugar phosphates was either equal or less in semen samples preserved in cold. CAW appeared to be a better extender than SKMEY as revealed by sugar uptake in cold.Acknowledgment. We are indebted to Dr D. Sundaresan, Director, for his kind encouragement in this study.     

In vitro dopaminergic neuroprotective and in vivo antiparkinsonian-like effects of Δ3,2-hydroxybakuchiol isolated from Psoralea corylifolia (L.)

Cocktail recipes containing Psoralea corylifolia seeds (PCS) are used to empirically treat Parkinson disease. A PCS isolate Δ³,2-hydroxybakuchiol (BU) can inhibit dopamine uptake in dopamine transporter (DAT) transfected Chinese hamster ovary (CHO) cells, and dopamine reuptake blockade may provide an alternative approach for ameliorating parkinsonism. Here, we assessed the potential dopaminergic neuroprotective, and antiparkinsonian-like activity of BU. BU sample size was increased by using a scale-up extraction paradigm. Pharmacologically, BU significantly protected SK-N-SH cells from 1-methyl-4-phenylpyridinium (MPP⁺) insult, produced striking inhibitory actions on dopamine/norepinephrine uptake and WIN35,428 binding in synaptosomes on in vivo administration, and significantly preventing poor performance on rotarod and dopaminergic loss in substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice. BU acts by protecting dopaminergic neurons from MPP⁺ injury and preventing against MPTP-induced behavioral and histological lesions in the Parkinson’s disease (PD) model, possibly by inhibiting monoamine transporters. These findings suggest that BU could be meaningful in PD treatment. Received 14 January 2009; received after revision 22 February 2009; accepted 10 March 2009     

Influence of progesterone on protein and RNA synthesis in cultured chick embryo liver cells

Summary Chick embryo liver primary cultures, when added with progesterone, exhibit, in comparison with the controls, a normal growth, a decline of both³H-uridine uptake and incorporation into total RNA, a decline of³H-leucine and¹⁴C serine incorporation into the proteins. Progesterone is not able to stimulate phosvitin synthesis induction.These studies were supported in part by the Italian CNR grants.     

Distribution of polychlorinated biphenyls: Structural requirements for accumulation in the mouse bronchial mucosa

Summary Autoradiography showed that labelled polychlorinated biphenyls with chlorine in positions 2, 4¹, 5 and hydrogen in positions 3, 3¹, 6, 6¹ in the molecule are accumulated in the mouse bronchial mucosa. Further testing of this observation showed that 2, 2¹, 4, 5¹-tetrachlorbiphenyl-¹⁴C, but not biphenyl-¹⁴C, was taken up in the bronchi of mice.This investigation was supported by the National Swedish Environment Protection Board.     

Preliminary studies of the metabolism of 2-guanidinomethyl-1:4-benzodioxan sulphate (guanoxan)

Resumen El sulfato de 2-guanidinometil-1:4-benzo-dioxano (guanidino¹⁴C) se sintetizó a partir del 2-aminometil-1: 4-benzodioxano y el sulfato de S-metiltiouronio (uronio¹⁴C). Un 52–53% de la dosis radioactiva administrada a los perros se recuperó en la orina en la forma de los siguientes compuestos radioactives:arginina, creatina, acido guanidino acético, creatinina, urea, 2-guanidinometil-1: 4-benzodioxano y un derivado hidroxilado (fenólico) del anterior. Se sintetizó tambien el sulfato de 2-guanidinometil-7-hidroxi-1:4-benzodioxano.     

The ischemic and postischemic effect on the uptake of neutral amino acids in isolated cerebral capillaries

Summary The uptake of some neutral amino acids was investigated in cerebral microvessels isolated from brains of gerbils subjected to bilateral cerebral ischemia with and without various periods of recovery. A transiently increased capillary uptake of³H-isoleucine,¹⁴C-cycloleucine and³H-phenylalanine was found in both conditions.     

Aberrant,canavanyl protein formation and the ability to tolerate or utilize L-canavanine

Summary L-Canavanine, 2-amino-4-(guanidinooxy)butyric acid, and L-arginine incorporation into de novo synthesized proteins was compared in six organisms. Utilizing L-[guanidinooxy¹⁴C]canavanine and L-[guanidino¹⁴C]arginine at substrate saturation, the canavanine to arginine incorporation ratio was determined in de, novo synthesized proteins.Caryedes brasiliensis andSternechus tuberculatus, canavanine utilizing insects;Canavalia ensiformis, a canavanine storing plant; and to a lesser extentHeliothis virescens, a canavanine resistant insect, failed to accumulate significant canavanyl proteins. By contrast,Manduca sexta, a canavanine-sensitive insect, andGlycine max, a canavanine free plant, readily incorporated canavanine into newly synthesized proteins. This study supports the contention that the incorporation of canavanine into proteins in place of arginine contributes significantly to canavanine's antimetabolic properties.     

Phagocytose des liposomes par les macrophages péritonéaux de souris

Summary Uptake of¹⁴C-cholesterol or³H-cholesterol labelled liposomes, stimulation of¹⁴C-glucose oxidation, as well as ultrastructural and autoradiographical experiments have shown that liposomes are phagocytized by mouse peritoneal macrophages. Further results have shown that degradation of liposomes was not complete 2 h after uptake.     

Thiamine transport by human intestine in vitro

Summary Surgical specimens of human gastrointestinal mucosa and muscle were incubated in vitro with thiaminethiazole-2-¹⁴C. Labelled thiamine uptake was uphill in mucosal tissues and downhill in muscle. Small intestinal mucosa accumulated labelled thiamine in a phosphorylated form, while gastric and colonic mucosa, as well as muscular layers of all gastrointestinal segments studied, did not.This work was supported in part by a grant from the Italian Research Council, Rome, Italy.     

Transfer of cantharidin (1) during copulation from the adult male to the femaleLytta vesicatoria (‘Spanish flies’)

Summary Adult males of the spanish flyLytta vesicatoria (Meloidae, Coleoptera) are able to biosynthesize cantharidin (1) in copula after injection of E, E-11-(³H,¹⁴C)-farnesol and 2-¹⁴C-methylfarnesoate. During mating, the cantharidin biosynthesized in the males is transferred to the females, who are unable to biosynthesize cantharidin from any terpenoid precursors. After injection of (³H,¹⁴C)-cantharidin into males during copulation, more than 10% is transferred into the female sex organs. Males injected with 2-(³H,¹⁴C)-mevalonate 24–30 h prior to copulation transferred 93–98% of the biosynthesized cantharidin to the females during mating. After mating, the males continue to produce cantharidin. It seems that in the male the biosynthesis of cantharidin is stimulated during copulation.III. Communication on the Biosynthesis of Cantharidin; II. Communication¹⁶.Dedicated to ProfessorKurt Mothes' (Halle/Saale, DDR) 75th birthday, 4.11.1975. J. R. Sierra, Thesis in preparation University Zürich. J. R. S. thanks the Eidgenössischen Stipendienkommission für ausländische Studierende for a fellowship.Research supported by the Schweizerische Nationalfonds.     

The mucopeptide turnover in the cell walls of growing cultures ofBacillus megaterium KM

Zusammenfassung Die Zellwände vonBacillus megaterium, in der Vorkultur durch 2-¹⁴C Diaminopimelinsäure (DAP) markiert, geben im Lauf ihrer weiteren Kultivierung DAP in den metabolischen «Pool» frei. Ein Teil der freigewordenen DAP wird zu¹⁴C Lysin dekarboxyliert und erscheint in Eiweiss inkorporiert. Aus dem Verhältnis der Radioaktivitäten in der Eiweiss- und in der Mucopeptidfraktion wurde die Geschwindigkeit des Mucopeptidumsatzes in den sich vermehrenden Zellen auf 3–4% in der Stunde festgestellt.     

Metabolism of the normal cardiovascular wall. 2. The pentose phosphate pathway

Riassunto La valutazione del¹⁴CO₂ derivante dal glucosio-1-¹⁴C e dal glucosio-6-¹⁴C ha dimostrato l'esistenza di una via metabolica attraverso il ciclo dei pentosi nelle arterie del cane, mentre questa non sembra essere presente nelle vene, nell'aorta e nel'miocardio.

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Investigation was conducted during tenure or Special Research Fellowship (No. 11091) U.S. Public Health Service.     

Interaction of CDP-choline with synaptosomal transport of biogenic amines and their precursors in vitro and in vivo in the rat corpus striatum

Summary Added to a striatal synaptosomal homogenate of rat brain, CDP-choline 10^–4 M inhibits the uptake of norepinephrine (NE), dopamine (DA) and serotonin (5 HT) in a competitive fashion and enhances the uptake of tyrosine and tryptophan; administered to animals, CDP-choline (50 mg/kg/l h/i.v.) inhibits only the in vitro uptake of DA but enhances the uptake of precursors.This research was supported by CNRS grant (ERA No. 560) and Inserm grant (FRA 5).     

Elimination and metabolism of dimethylnitrosamine (DMN) byXenopus laevis and other amphibians

Summary The elimination of (¹⁴C)-DMN after i.p. injection intoXenopus was measured, as was the metabolism in vitro of (¹⁴C)-DMN by liver fromXenopus and 9 other amphibian species. In view of its rapid elimination from the body and low rate of metabolism byXenopus liver in vitro, DMN is unlikely to be toxic or carcinogenic inXenopus.This work was supported by a grant from the Cancer Research Campaign. We are also grateful to Dr P. F. Swann, both for the supply of DMN and DEN and for many useful discussions.