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.
Aiken
S P
SP
Department of Pharmacology and Toxicology, New Jersey Medical School (UMDNJ), Newark 07103-2714.
Sellin
L C
LC
Schmidt
J J
JJ
Weinstein
S A
SA
McArdle
J J
JJ
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