The presynaptic activity of bothropstoxin-I, a myotoxin from Bothrops jararacussu snake venom.
Bothropstoxin-I from Bothrops jararacussu snake venom is a lysine-49 phospholipase A(2) with myotoxic and neurotoxic activities. In this study, we used mouse phrenic nerve-diaphragm preparations in the absence and presence of manganese (Mn(2+)), a presynaptic blocker, to investigate a possible presynaptic action of bothropstoxin-I. At concentrations of 0.9 mM and 1.8 mM, Mn(2+) produced 50% neuromuscular blockade in less than 4 min., which was spontaneously reversible at the lower concentration. Bothropstoxin-I (1.4 microM) irreversibly inhibited neuromuscular blockade by 50% in 31+/-4 min. (mean+/-S.E.M., n = 9). Pretreating preparations with 0.9 mM Mn(2+) prevented the blockade by bothropstoxin-I. When added after bothropstoxin-I, Mn(2+) produced its characteristic blockade and, after washing, the twitch tension returned to pre-Mn(2+) levels, indicating that bothropstoxin-I caused irreversible damage before the addition of Mn(2+). Electrophysiological measurements showed that a concentration of bothropstoxin-I (0.35 microM), which did not produce neuromuscular blockade, caused the appearance of giant miniature end-plate potentials with no change in the membrane resting potential but increased the quantal content. Preparations preincubated with Mn(2+) (0.9 mM, 30 min.) were protected against the depolarizing action of bothropstoxin-I (0.7 microM). These results show that, in addition to its well-known myotoxic effect, bothropstoxin-I also has a presynaptic action.
Oshima-Franco
Yoko
Y
Department of Pharmacology, Faculty of Medical Sciences, Institute of Biology, State Univeristy of Campinas (UNICAMP), 13083-970, Campinas, SP, Brazil.
Leite
Gildo Bernardo
GB
Belo
Cháriston André Dal
CA
Hyslop
Stephen
S
Prado-Franceschi
Júlia
J
Cintra
Adélia Cristina Oliveira
AC
Giglio
José Roberto
JR
da Cruz-Höfling
Maria Alice
MA
Rodrigues-Simioni
Léa
L
D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D008345:Manganese / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D019148:Neuromuscular Blockade; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D003435:Crotalid Venoms; D009466:Neuromuscular Blocking Agents; C078097:bothropstoxin; D008345:Manganese