Dendrotoxin from the venom of the green mamba, Dendroaspis angusticeps - a neurotoxin that enhances acetylcholine release at neuromuscular junctions

A. L. Harvey, E. Karlsson

Research output: Contribution to journalArticlepeer-review

141 Citations (Scopus)

Abstract

The venom of the green mamba, Dendroaspis angusticeps has previously been shown to produce neuromuscular facilitation by increasing acetylcholine release. After gel filtration and ion-exchange chromatography of the whole venom, a basic polypeptide with facilitatory actions was isolated. This polypeptide, named dendrotoxin, has 59 amino acid residues, probably with only 3 disulphide bonds and a blocked N-terminus. When injected into conscious mice, dendrotoxin made the mice hypersensitive to external stimuli and subsequently produced respiratory paralysis. When tested on the isolated chick biventer cervicis nerve-muscle preparation, concentrations of dendrotoxin of 0.5 μg/ml (7×10-8 M) and greater, increased responses to indirect stimulation by 200-250%, without any increase in responses to submaximal concentrations of exogeneous acetylcholine, carbachol, KCl or direct stimulation. The augmentation was slow to develop, not reversed by washing, and could last several hours before slowly waning. Dendrotoxin did not produce spontaneous twitching or contractures. It is concluded that dendrotoxin is not an anticholinesterase, does not affect receptor sensitivity or muscle contractility, but produces twitch augmentation by increasing the amount of acetylcholine released by nerve stimulation. Thus, dendrotoxin appears to represent a snake venom neurotoxin with unusual chemical and pharmacological properties.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume312
Issue number1
DOIs
Publication statusPublished - 1 May 1980

Keywords

  • acetylcholine release
  • dendroaspis angusticeps
  • neuromuscular facilitation
  • neurotoxins
  • snake venoms
  • acetylcholine
  • dendrotoxin
  • potassium chloride
  • animal experiment
  • dose response
  • intraperitoneal drug administration
  • neuromuscular transmission
  • peripheral nervous system

Cite this