Toosendanin interferes with pore formation of botulinum toxin type A in PC12 cell membrane.

Abstract

AIM:

Botulinum neurotoxins (BoNT) abort the process of neurotransmitter release at presynaptic motor nerve terminals, causing muscle paralysis. The ability of botulinum toxin to produce its effect is dependent on the ability of the light chain to cleave the SNARE proteins associated with transmitter release. Translocation of the light chain protease through the heavy chain-formed channel is a pivotal step in the intoxication process. Toosendanin (TSN), a triterpenoid derivative extracted from a Chinese traditional medicine, has been demonstrated to be an effective cure for experimental botulism. This study was designed to explore the antibotulismic mechanisms of toosendanin.

METHODS:

The inside-out single-channel recording patch-clamp technique was used to record the BoNT/A-induced currents in the presence and absence of TSN.

RESULTS:

Channel formation was delayed and the sizes of the channels were reduced in the TSN-treated PC12 cell membrane.

CONCLUSION:

The antibotulismic effect of TSN might occur via interference with toxin translocation.

• Authors: Mu-feng Li, Yu-liang Shi
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 27 Issue 1 Pg. 66-70 (Jan 2006) ISSN: 1671-4083 [Print] United States
• PMID: 16364212 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• Ion Channels
• toosendanin
• Botulinum Toxins, Type A

Topics

• Animals
• Botulinum Toxins, Type A (antagonists & inhibitors, metabolism)
• Cell Membrane (drug effects, physiology)
• Drugs, Chinese Herbal (isolation & purification, pharmacology)
• Ion Channels (drug effects)
• Melia (chemistry)
• PC12 Cells
• Plants, Medicinal (chemistry)
• Protein Transport
• Rats