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Clostridium Neurotoxins Influence Serotonin Uptake and Release Differently in Rat Brain Synaptosomes
Author(s) -
Najib Abderrahim,
Pelliccioni Patricia,
Gil Carles,
Aguilera José
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0721991.x
Subject(s) - serotonin , neurotoxin , chemistry , 5 ht receptor , biochemistry , pharmacology , biology , receptor
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 Zn 2+ ‐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 Zn 2+ ‐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 IC 50 of H C ‐TeTx ranges from 0.62 to 2.08 n M . Binding of [ 3 H]imipramine and [ 3 H]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.