Toxins from mamba venoms that facilitate neuroiluscular transmission

A. L. Harvey, A. J. Anderson, P. M. Mbugua, E. Karlsson

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Venoms from the four species of African mambas have many neurotoxins that are different from other snake neurotoxins. Postjunctional αneurotoxins, which bind to nicotinic cholinoceptors, appear to be the only type of toxin that mambas have in common with other snakes with neurotoxic venoms. Typical mamba neurotoxins are prejunctional facilitatory toxins and anticholinesterase toxins or fasciculins. The prejunctional facilitatory toxins enhance the amount of transmitter that is released in response to nerve stimulation. This activity was first demonstrated with dendrotoxin (from Dendroaspis anqusticeps) at the neuromuscular junction, but it can also be observed in both the sympathetic and parasympathetic branches of the autonomic nervous system and in the central nervous system. These facilitatory neurotoxins have 57-60 amino acids in a single polypeptide chain cross-linked by three disulphide bonds. They are structurally homologous to the Kunitz type protease inhibitors such as bovine pancreatic trypsin inhibitor. The anticholinesterase toxins are specific and powerful in inhibitors (Ki of about 10-10 M) of acetylcholinesterase from several sources (human erythrocytes, rat brain and muscle, eel electroplax) but they have no effect on acetylcholinesterase from cobra venom or chick brain and muscle. The first two of these inhibitors (from Dendroaspis angusticeps) were called fasciculins because of the long-lasting muscle fasciculations that they produced in mice. Fasciculins have 61 amino acids and four disulphides and show sequence homology with the postjunctional short neurotoxins. Synergistic interactions between components are characteristic of mamba venoms. One of these components is always a member of the so-called "angusticeps-type" toxins (short neurotoxin homologues of 58-60 amino acids and four disulphides). These toxins are divided into four subgroups, the anticholinesterases constituting subgroup I. Angusticeps-type toxins interact with facilitatory toxins or with so-called "synergistic-type" proteins (toxins of two subunits, each with 62-63 amino acids and joined together by disulphide bonds). The pharmacology of these interactions is not known, only data on the increased lethality of the synergistic mixtures is available.

Original languageEnglish
Pages (from-to)91-137
Number of pages47
JournalToxin Reviews
Volume3
Issue number2-3
DOIs
Publication statusPublished - 1 Jan 1984

Keywords

  • acetylcholine
  • carbachol
  • dendrotoxin
  • neurotoxin
  • nicotine
  • noradrenalin
  • snake venom
  • autonomic nervous system
  • drug efficacy
  • drug toxicity
  • intoxication
  • mambatoxin
  • muscle
  • neuromuscular transmission

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  • Cite this

    Harvey, A. L., Anderson, A. J., Mbugua, P. M., & Karlsson, E. (1984). Toxins from mamba venoms that facilitate neuroiluscular transmission. Toxin Reviews, 3(2-3), 91-137. https://doi.org/10.3109/15569548409097923