A novel peptide toxin from Trimeresurus wagleri acts pre- and post-synaptically to block transmission at the rat neuromuscular junction.
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.
Department of Pharmacology and Toxicology, New Jersey Medical School (UMDNJ), Newark 07103-2714.
S P
SP
Aiken
L C
LC
Sellin
J J
JJ
Schmidt
S A
SA
Weinstein
J J
JJ
McArdle
D000818:Animals; D003435:Crotalid Venoms / Q000494:pharmacology*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011789:Quantum Theory; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014118:Toxins, Biological / Q000494:pharmacology*
D003435:Crotalid Venoms; D009466:Neuromuscular Blocking Agents; D018377:Neurotransmitter Agents; D014179:Neurotransmitter Uptake Inhibitors; D010455:Peptides; D014118:Toxins, Biological