Autor: S. I. Walaas, Thor Willy Ruud Hansen, Siri B.W Mathiesen, Iren Sefland
Rok vydání: 1999
Předmět:
Zdroj: Neurochemical Research. 24:733-738
ISSN: 0364-3190
DOI: 10.1023/a:1020775312214
Popis: 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.
Databáze: OpenAIRE