Premium
The Presynaptic Activity of Bothropstoxin‐I, a Myotoxin from Bothrops jararacussu Snake Venom
Author(s) -
OshimaFranco Yoko,
Leite Gildo Bernardo,
Belo Cháriston André Dal,
Hyslop Stephen,
PradoFranceschi Júlia,
Cintra Adélia Cristina Oliveira,
Giglio José Roberto,
Da CruzHöfling Maria Alice,
RodriguesSimioni Léa
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.pto_950405.x
Subject(s) - myotoxin , blockade , neuromuscular blockade , bothrops , chemistry , venom , depolarization , electrophysiology , phrenic nerve , neuromuscular junction , pharmacology , phospholipase , neuromuscular transmission , biophysics , anatomy , anesthesia , endocrinology , medicine , snake venom , biochemistry , respiratory system , biology , receptor , enzyme , neuroscience
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 μM) 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 μM), 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 μM). These results show that, in addition to its well‐known myotoxic effect, bothropstoxin‐I also has a presynaptic action.