A novel depolarizing activity of scorpion venom fraction M1 due to activation of skeletal muscle nicotinic receptors.

Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis BP 74-1002, Tunisia.
Toxicon (Impact Factor: 2.92). 02/2007; 49(1):117-22. DOI: 10.1016/j.toxicon.2006.09.011
Source: PubMed

ABSTRACT A depolarizing activity following interaction with nicotinic acetylcholine receptors (nAchRs) in skeletal muscle cells, was observed for the first time in the non-toxic venom fraction (M1) of the yellow scorpion Buthus occitanus tunetanus (Bot). The effects of M1 fraction were tested on cultured rat myotubes by recording changes in [Ca2+]i. When applied, M1 (10 microg/mL) induced a transient increase of [Ca2+]i which could be blocked by a prior application of alpha-Bungarotoxin (alpha-Bg-Tx).

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Running title: Massive autonomic stimulation by Venezuelan scorpion venoms. Título corto: Estimulación autonómica masiva producida por los venenos de escorpiones venezolanos. Venezuelan scorpion envenomation is a public health problem produced by Tityus discrepans (TD) and Tityus zulianus (TZ) species. Patients envenomend by TD developed gastrointestinal and pancreatic disorders and scorpion accidents involving TZ are associated with high mortality rate, which showed cardiopulmonary clinical disorders may be associated to the high levels of plasma catecholamines levels. This distinctive clinical output seems to be associated to a toxin repertoire diversity, which has been previously demonstrated. Trying to mimic the human envenomation, some toxinological studies have been performed using TD and TZ venoms in several biomodels such as mice and anesthetized rams. The purpose of this study was to evaluate, in vivo using biomodels (mice), the role of autonomic nervous system (sympathetic) stimulation producing some of the clinical signs, via the catecholamines release, on the patho-physi-ology of the TZ and TD induced envenomation. Thus, a clinical signs here reported during a period of 1 hr, after a single intra-peritoneal injection of sub-lethal doses of TZ or TD venom, which are related with diarrhea, diaphoresis, intense salivation, dehydratation, dyspnea and spasticity in hind limbs. However, these animals did not exhibit vomiting, which is frequent in humans envenomed by TD. All animals inoculated with TD or TZ venoms developed diarrhea, being more pronounced in TD group. Diaphoresis, sialorrhea and dehydratation were mainly observed in TD group. Dyspnea and the hind limb spasticity were only developed in TZ mice. These clinical manifestations (diarrhea, sialorrhea, dehydra-tation and intense salivation) are related to an activation of autonomic nervous system, via an intense release of their related neurotransmitters. Thus, autonomic stimulation (sympathetic) was evaluated following the catecholamine (Nor-Epinephrine)(NE) plasma levels in a function of envenomation time. We found a significant increments at 1 hr, after venom injection, in more than 640% in NE plasma levels for TZ venom while in TD group, around 520% rise in NE concentrations were detected. This massive rise in NE concentrations in TZ- and TD-envenomed mice decreased at 6 hrs but remained higher until 24 hrs for both venoms in comparison with Control animals. However, these catecholamines plasma alterations do not explain the dyspnea and hind limb spasticity and more toxinological research should be done to understand the molecular mechanisms related to last clinical signs.
    Archivos Venezolanos de Farmacologia y Terapeutica 01/2012; 31(1):1-6.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scorpion envenoming is less studied in pregnant victims. In this work, the effect of Buthus occitanus tunetanus on parturition in late pregnancy was studied in an animal model. Four groups of six primigravid female rats, each one at the 22nd day of pregnancy, were used. The first two groups had received an intra-peritoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom or a physiological saline solution and left until foetal delivery. Then, the time elapsed until the first pup delivery and that separating the first and latest ones were measured. The other two groups served for the uterine electrophysiological activity exploration. Rats were anaesthetized, artificially ventilated and had received an intraperitoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom or a physiological saline solution. Our results showed a significant increase of the latency to foetal delivery, labour time, and uterine contractile activity in envenomed rats compared to controls. Such signs are usually seen in dynamic dystocia. It was concluded that Buthus occitanus tunetanus envenoming might induce a dynamic dystocia, when it occurred in late pregnancy.
    Comptes Rendus Biologies 01/2008; 330(12):890-6. · 1.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scorpion envenomation is a public health problem in Venezuela, mainly produced by Tityus discrepans (TD) and Tityus zulianus (TZ). Accidents by these two species differ clinically. Thus, TZ envenomation is associated with high mortality in children due to cardiopulmonary disorders, as a result of, excessive amounts of plasma catecholamines (Epinephrine) release from adrenal medulla, probably via the voltage-gated sodium-channel activated by specific scorpion toxins. This Epi release is, in part responsible, for some of the envenomation clinical consequences, resembling those described for patients presenting catecholamine-releasing tumors (pheochromocytoma). In this work, BALB/c mice and rat pheochromocytoma-derived PC12 cells were used to provide in vivo and in vitro models, respectively, on which the basis for the TZ-mediated catecholamine release mechanism could be elucidated. In mice, TZ venom increased, at 1h post-injection, the Epi plasma levels in 4000%, which remained elevated for 24h. A significant rise in plasma levels of the catecholamine catabolite 3-Methoxy-4-Hydroxy-Phenyl-Glycol (MHPG) was also observed. In [(3)H]dopamine-loaded PC12 cells, TZ venom potentiated the carbamylcholine (CC)-mediated release of [(3)H]dopamine, as shown by the leftward shift in the CC-dose-response curves. Moreover, TZ venom also displayed the maximal [(3)H]dopamine releasing activity compared to TD venom, with significant reduction of the EC50 for CC. The nicotinic-acetylcholine receptor (nAChR) blocker hexamethonium induced a significant inhibition of the [(3)H]dopamine release produced by CC in PC12 cells but the TZ-elicited release of [(3)H]dopamine was 70% hexamethonium-insensitive, suggesting unidentified TZ toxins affecting other regulatory mechanisms of catecholamine secretion.
    Toxicon 11/2011; 59(1):117-23. · 2.92 Impact Factor


Available from
May 22, 2014