Clostridium neurotoxins influence serotonin uptake and release differently in rat brain synaptosomes

Abderrahim Najib, Patricia Pelliccioni, Carles Gil, José Aguilera

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

Clostridium neurotoxins produce inhibition of both basal and K+-evoked serotonin release in rat brain synaptosomes. To produce these effects, tetanus toxin (TeTx), as well as botulinum neurotoxin type A (BoNT/A), added to brain synaptosomes, must be incubated at 37°C over a long interval (hours). This serotonin exocytosis inhibition was abolished with previous treatment with specific Zn2+-metalloprotease inhibitors. Nevertheless, a short incubation time produces different behavior of the indicated neurotoxins: TeTx significantly blocks the sodium-dependent, high-affinity serotonin uptake, whereas a small increase of this uptake was found with BoNT/A. Both Zn2+-metalloprotease active fragments, light chains of TeTx and BoNT/A, are unable to reproduce the block of the serotonin uptake, whereas the C-terminal portion of the TeTx heavy chain (H(C)-TeTx), which binds specifically to the target tissue, inhibited the serotonin uptake in a dose-dependent manner. The IC50 of H(C)TeTx ranges from 0.62 to 2.08 nM. Binding of [3H]imipramine and [3H]serotonin did not change after toxin treatments, which indicates that these clostridium neurotoxins do not act on the serotonin high-affinity site at the serotonin transporter or at other serotonin high-affinity sites. These results could indicate that TeTx and H(C)-TeTx bind to different targets than BoNT/A in the plasma membrane.
Original languageEnglish
Pages (from-to)1991-1998
JournalJournal of Neurochemistry
Volume72
DOIs
Publication statusPublished - 28 Apr 1999

Keywords

  • 5-hydroxytryptamine (serotonin)
  • Botulinum neurotoxin type A
  • Clostridium neurotoxin
  • Release
  • Tetanus toxin
  • Uptake
  • [ h]imipramine binding 3

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