Presence of curarizing polypeptides and a pancreatitis-inducing fraction without muscarinic effects in the venom of the Venezuelan scorpion Tityus discrepans (Karsch).
Four toxic polypeptidic fractions (TdF-I-IV) were purified from the venom of the Venezuelan scorpion Tityus discrepans by means of gel filtration on Sephadex G'-50. The peptides have mol. wts of approx. 6000 and normalized elution volumes (Vn = Elution volume/Total column volume) of: TdF-I = 0.27 (0.26, 0.28), n = 13; TdF-II = 0.40 (0.39, 0.41), n = 15; TdF-III = 0.57 (0.56, 0.59), n = 14, and TdF-IV = 0.68 (0.67, 0.70), n = 13 (median and its 95% confidence interval, n = number of elutions used to calculate the median). Mice (white, male, 16-19 g, IVIC strain) were injected with these fractions and sacrificed 48 hr later. No toxicity was observed when fraction I (0.93 microgram/g mice) or IV (2.51 micrograms/g mice) was injected i.p. into mice. TdF-II (9 to 50 micrograms/g mice) produced sialorrhea, dyspnea and death 1 hr after i.p. injection. Light microscopy of the pancreas revealed that TdF-III (3.42 micrograms/g mice) produced structural modifications such as acinar cell vacuolization, degranulation and interstitial swelling; these changes are characteristic of acute pancreatitis. No effects on the islets of Langerhans or the pancreatic ducts were observed. TdF-III had no overt muscarinic effects when injected i.p. into mice. On the neuromuscular preparation of the frog (Hyla crepitans) TdF-I blocked neuromuscular transmission at the postsynaptic membrane; TdF-II depolarized the muscle membrane by opening sodium channels and TdF-IV prolonged action potentials, suggesting potassium channel blockage.
D'Suze
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Laboratory of Cellular Neuropharmacology, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas, Venezuela.
Sevcik
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Ramos
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001001:Anura; D005591:Chemical Fractionation; D002850:Chromatography, Gel; D004594:Electrophysiology; D007274:Injections, Intraperitoneal; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000032:analysis* / Q000633:toxicity; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced*; D010455:Peptides / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity; D015221:Potassium Channels / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D015222:Sodium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D009467:Neuromuscular Depolarizing Agents; D010455:Peptides; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D012604:Scorpion Venoms; D015222:Sodium Channels