Bilirubin Inhibits Ca2+-Dependent Release of Norepinephrine from Permeabilized Nerve Terminals View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-06

AUTHORS

Thor Willy Ruud Hansen, Siri B.W. Mathiesen, Iren Sefland, S. Ivar Walaas

ABSTRACT

Although the well-known neurotoxic agent bilirubin can induce alterations in neuronal signaling, direct effects on neurotransmitter release have been difficult to demonstrate. In the present study we have used permeabilized nerve terminals (synaptosomes) from rat brain prelabeled with [3H]norepinephrine to examine the effects of bilirubin on transmitter release. Rat cerebrocortical synaptosomes were permeabilized with streptolysin-O (2 U/ml) in the absence or presence of bilirubin (10 microM-320 microM) and Ca2+ (100 microM), and the amount of radiolabeled transmitter released during 5 min to the medium was analysed. Low levels of bilirubin decreased Ca2+-evoked release in a dose-dependent manner, with half-maximal effect at approx 25 microM bilirubin. Higher levels of bilirubin (100-320 microM) increased [3H]norepinephrine efflux in the absence of Ca2+, suggesting that high bilirubin levels induced leakage of transmitter from vesicles. The nontoxic precursor biliverdin had no effect on Ca2+-dependent exocytosis. Our data indicate that bilirubin directly inhibits both exocytotic release and vesicular storage of brain catecholamines. More... »

PAGES

733-738

References to SciGraph publications

  • 1993-02. Interactions of bilirubin with isolated presynaptic nerve terminals: Functional effects on the uptake and release of neurotransmitters in CELLULAR AND MOLECULAR NEUROBIOLOGY
  • 1989-10. The Effects of Bilirubin on Brain Energy Metabolism during Hyperosmolar Opening of the Blood-Brain Barrier: An In Vivo Study Using 31P Nuclear Magnetic Resonance Spectroscopy in PEDIATRIC RESEARCH
  • 1988-02. Bilirubin Decreases Phosphorylation of Synapsin I, a Synaptic Vesicle-Associated Neuronal Phosphoprotein, in Intact Synaptosomes from Rat Cerebral Cortex in PEDIATRIC RESEARCH
  • 1995-06. The synaptic vesicle cycle: a cascade of protein–protein interactions in NATURE
  • 1988-05. Short-Term Exposure to Bilirubin Reduces Synaptic Activation in Rat Transverse Hippocampal Slices in PEDIATRIC RESEARCH
  • 1996-06. Bilirubin Has Widespread Inhibitory Effects on Protein Phosphorylation in PEDIATRIC RESEARCH
  • 1998-09. Bilirubin Inhibits Transport of Neurotransmitters in Synaptic Vesicles in PEDIATRIC RESEARCH
  • 1989-11. Inhibition of noradrenaline release by antibodies to B-50 (GAP-43) in NATURE
  • 1956-12. Bilirubin, an Uncoupler of Oxidative Phosphorylation in Isolated Mitochondria in NATURE
  • 1992-11. Changes in Piglet Auditory Brainstem Response Amplitudes without Increases in Serum or Cerebrospinal Fluid Neuron-Specific Enolase in PEDIATRIC RESEARCH
  • 1995-12. Bilirubin Induces a Calcium-Dependent Inhibition of Multifunctional Ca2+/Calmodulin-Dependent Kinase II Activity in Vitro in PEDIATRIC RESEARCH
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/a:1020775312214

    DOI

    http://dx.doi.org/10.1023/a:1020775312214

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10447456


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