A novel peptide toxin from Trimeresurus wagleri acts pre- and post-synaptically to block transmission at the rat neuromuscular junction

Pharmacol Toxicol. 1992 Jun;70(6 Pt 1):459-62. doi: 10.1111/j.1600-0773.1992.tb00508.x.

Abstract

The neuromuscular effects of a peptide toxin (peptide I) from venom of Trimeresurus wagleri were investigated using the rat extensor digitorum longus muscle/peroneal nerve preparation. Sub-micromolar concentrations depressed endplate currents (EPCs) produced in response to nerve stimulation. Since quantal content of EPCs was not altered, it appears that the site of action is post-synaptic. However, higher concentrations (1.4-2.9 microM) also inhibited spontaneous release of transmitter. Nerve stimulation in the presence of peptide I caused 'rundown' of EPC amplitude, evidence that the peptide acts pre-synaptically to interfere with transmitter release. Recovery from this effect occurred within 3-5 min. of washing, but EPC amplitude took 20-30 min. to recover. The dual action of this peptide makes it unusual amongst naturally-occurring toxins, and these data suggest that further investigation of the peptide (and its analogues) could yield new information about neurotransmitter release.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Crotalid Venoms / pharmacology*
  • Electrophysiology
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Male
  • Membrane Potentials / drug effects
  • Motor Endplate / drug effects
  • Motor Endplate / physiology
  • Neuromuscular Blocking Agents / pharmacology*
  • Neuromuscular Junction / drug effects*
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Peptides / pharmacology*
  • Quantum Theory
  • Rats
  • Rats, Wistar
  • Synapses / drug effects*
  • Synapses / metabolism
  • Synapses / physiology
  • Synaptic Transmission / drug effects*
  • Toxins, Biological / pharmacology*

Substances

  • Crotalid Venoms
  • Neuromuscular Blocking Agents
  • Neurotransmitter Agents
  • Neurotransmitter Uptake Inhibitors
  • Peptides
  • Toxins, Biological