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

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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 μM–320 μM) and Ca2+ (100 μM), 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 μM bilirubin. Higher levels of bilirubin (100–320 μM) 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.

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Author notes

  1. Thor Willy Ruud Hansen

    Present address: Department of Pediatrics, The National Hospital, N-0027, Oslo, Norway

Authors and Affiliations

  1. Neurochemical Laboratory, Department Group of Basic Medical Sciences, University of Oslo, N-0317, Oslo, Norway

    Thor Willy Ruud Hansen, Siri B.W. Mathiesen, Iren Sefland & S. Ivar Walaas (MD, PhD)

  2. Neonatal Critical Care, Department of Anesthesia and Critical Care Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh, PA

    Thor Willy Ruud Hansen

  3. Neurochemical Laboratory, University of Oslo, Oslo, Norway

    S. Ivar Walaas (MD, PhD)

Authors
  1. Thor Willy Ruud Hansen
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  2. Siri B.W. Mathiesen
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  3. Iren Sefland
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  4. S. Ivar Walaas
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Hansen, T.W.R., Mathiesen, S.B., Sefland, I. et al. Bilirubin Inhibits Ca2+-Dependent Release of Norepinephrine from Permeabilized Nerve Terminals. Neurochem Res 24, 733–738 (1999). https://doi.org/10.1023/A:1020775312214

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