Development of noradrenaline uptake in the human foetal heart

Summary The development of NA-uptake mechanisms in the human foetal heart start at the same time as the adrenergic terminals were visible. The highest³H-NA values in the human foetal heart were only 25–30% of those found in the mouse heart.Acknowledgment. The technical assistance of Miss Marjo Martonen is gratefully acknowledged. This investigation was supported by a grant from the National Research Council for Medical Science, Finland.     

Structure-activity relationship of various ephedrine isomers on noradrenaline uptake by the isolated perfused rabbit heart]

(-)Ephedrine, (+) Ephedrine, (-) psi ephedrine and (+) psi ephedrine inhibit both the neuronal and extraneuronal uptakes of noradrenaline in isolated Rabbit heart. (-) ephedrine is the most active isomer for the inhibition of both neuronal and extraneuronal uptakes. The relative inhibition potential of the three other isomers is not the same when applied to one or other uptake.     

A possible mechanism for uptake of biogenic amines by storage organelles: Incorporation into nucleotide-metal aggregates

Zusammenfassung Analytische Ultrazentrifugation ergibt, dass Adenosin-5-triphosphat und Guanosin-5-triphosphat in Gegenwart von Ca und Mg hochmolekulare Aggregate bilden. Die scheinbaren mittleren Molekulargewichte dieser Aggregate nehmen nach Zusatz von 5-Hydroxytryptamin oder Noradrenalin stark zu. Es wird daraus geschlossen, dass Nucleotidaggregate biogene Amine inkorporieren, wobei Nucleotid-Aminaggregate entstehen. Dies erklärt möglicherweise die Aufnahme und Speicherung von biogenen Aminen in nucleotidhaltigen subzellulären Organellen, z.B. von Blutplättchen, Nebennierenmark und noradrenergen Nerven.     

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na⁺ channels and amplitude of Ca⁺⁺ currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases.     

A quantitative method for measuring the uptake of colloidal carbon by mouse tissues

Résumé On décrit une méthode spectrophotométrique quantitative pour la détermination de la répartition du carbone colloÏdal dans les organes d'une seule souris. La sensibilité de la méthode est de 0,25l de la suspension de carbone colloÏdal C11/1431a. La rate est le tissu qui a présenté la plus grande capacité de fixation du carbone. Elle est suivie par la moelle osseuse, la foie et les poumons.     

In vivo degradation of noradrenaline by MAO A in locus coeruleus of the rat

Depletion of noradrenaline in locus coeruleus neurons after reserpinization was prevented by clorgyline, a selective inhibitor of MAO A, but not by deprenyl, a selective inhibitor of MAO B. Only MAO A is therefore responsible for the degradation of homoneuronal noradrenaline in locus coeruleus nerve cells.     

Influences of cell cycle on uptake of SV40-DNA by diploid human cells

Zusammenfassung Autoradiographische Untersuchungen an menschlichen, diploiden, synchronisierten Zellen, in der S-Phase mit Tritium markiertem SV40 infiziert, zeigten intranukleären Einbau von markierter DNS (in Metaphase vor allem Chromosomenmarkierung). Keinerlei Kernmarkierung wurde beobachtet, wenn die Zellen in anderen Phasen ihres Zyklus infiziert wurden.

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This work was supported, in part, by a grant from the James W. McLaughlin Fund. Our thanks are due to Dr.K. G. Weiss for the valuable help in preparing the German summary.     

Ectoprotein kinase-mediated phosphorylation of FAT/CD36 regulates palmitate uptake by human platelets

Glycoprotein IV (FAT/CD36) has been shown to be phosphorylated by a cAMP-dependent, platelet membrane-bound ectokinase. In this study, we demonstrate that ectophosphorylation of FAT/CD36 regulates initial palmitate uptake. This is the first time that short-term regulation of the activity of a long-chain fatty acid carrier could be shown. Phosphorylation of FAT/CD36 was paralleled by a significant decrease in initial palmitate uptake by morphologically and functionally intact platelets. Maximum inhibition of palmitate uptake was achieved at 0.5 nM extracellular ATP, being significantly decreased to 72% compared to the control. Inhibition of palmitate uptake was abolished by co-incubation with the specific protein kinase A inhibitor peptide PKI or with β,γ-methylene-ATP, and was reversible upon addition of alkaline phosphatase. An extracellular ATP concentration above 5 μM completely prevented the ectophosphorylation-mediated inhibition of palmitate uptake. We conclude that FAT/CD36-mediated palmitate uptake by human platelets is short-term regulated via cAMP-dependent ectophosphorylation of FAT/CD36. Received 18 July 2002; received after revision 29 August 2002; accepted 19 September 2002 RID="*" ID="*"Corresponding author.     

The human leukemia cell line,THP-1: A multifacetted model for the study of monocyte-macrophage differentiation

Summary THP-1 is a human monocytic leukemia cell line. After treatment with phorbol esters, THP-1 cells differentiate into macrophage-like cells which mimic native monocyte-derived macrophages in several respects. Compared to other human myeloid cell lines, such as HL-60, U937, KG-1, or HEL cell lines, differentiated THP-1 cells behave more like native monocyte-derived macrophages. Because of these characteristics, the THP-1 cell line provides a valuable model for studying the mechanisms involved in macrophage differentiation, and for exploring the regulation of macrophage-specific genes as they relate to physiological functions displayed by these cells.     

Asialoprotein uptake by liver cells: immunofluorescence microscopy.

Uptake of asialoproteins by hepatocytes causes a change in the intracellular pattern of immunofluorescence. Control cells display a peripheral fluorescence which probably represents nascent proteins. Dark nonfluorescent areas, that presumably contain glycogen, are located around the nucleus. In contrast, liver cells from rats injected with asialoproteins display a pancytoplasmic fluorescence due to an influx of endocytotic vesicles.     

Influence of coronary dilators on the uptake of serotonin by human platelets and adrenaline by chromaffine granules

Zusammenfassung In einer unspezifischen, physikalisch-chemischen Wirkung von vier oberflächenaktiven Coronardilatatoren auf die Membranen von menschlichen Thrombozyten und isolierten chromaffinen Granula wird die Ursache für die Hemmung der Aufnahme von Serotonin bzw. Adrenalin erblickt.     

Bactericidal activity againstPseudomonas aeruginosa is acquired by cultured human monocyte-derived macrophages after uptake of myeloperoxidase

Myeloperoxidase (MPO) is an enzyme located within polymorphonuclear neutrophils capable of producting cytotoxic oxidant species that are particularly active against bacteria with polysaccharide capsules.Pseudomonas aeruginosa (10⁶ bacteria per 1 ml) are killed within 1 h in vitro by a MPO/H₂O₂/Cl^– system (48 mU=132 ng of MPO). The question arose as to whether human macrophages would acquire cytotoxic activity when loaded with this enzyme. Monocytes were therefore isolated from human blood and cultured for up to ten days to induce maturation to macrophages. These cells lost endogenous MPO within five days while H₂O₂ production in response to stimulation by phorbol myristate acetate (10^–6M) decreased to 23% within ten days. On the other hand, their capacity to take up exogenous MPO increased fourfold from day three to day ten. Human macrophages cultured from eight days (when both H₂O₂ production and MPO uptake were sufficient) were therefore used to study the effects of MPO uptake on cytocidal activity againstPseudomonas aeruginosa. After a 1 h MPO loading period, macrophages (5×10⁵ cells per ml) were incubated in the presence of bacteria (0.5 to 2×10⁶ bacteria per ml) for 2 h at 37°C. At a bacteria/macrophage ratio of 1, only 34.8±7.0% of bacteria survived (compared to killing by non-loaded macrophages), while 74.4±9.3% survived at a ratio of 4. From these results, we conclude that loading macrophages with exogenous MPO could enhance their microbicidal activity, suggesting a potentially useful therapeutic application.