title: Toosendanin interferes with pore formation of botulinum toxin type A in PC12 cell membrane.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The antibotulismic effect of TSN might occur via interference with toxin translocation.
authors.affiliation: Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai.
authors.forename: Mu-feng
authors.initials: MF
authors.lastname: Li
authors.forename: Yu-liang
authors.initials: YL
authors.lastname: Shi
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D031585:Melia / Q000737:chemistry; D016716:PC12 Cells; D010946:Plants, Medicinal / Q000737:chemistry; D021381:Protein Transport; D051381:Rats; D014315:Triterpenes
chemical_list: D019274:Botulinum Toxins, Type A; D004365:Drugs, Chinese Herbal; D007473:Ion Channels; C036454:toosendanin; D014315:Triterpenes