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(R) G-50. The peptides have mol. wts of approx. 6000 and normalized elution volumes (V-n = 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, 16-19g, IVIC strain) were injected with these fractions and sacrificed 48 hr later. No toxicity was observed when fraction I (0.93 mu g/g mice) or IV (2.51 mu g/g mice) was injected i.p. into mice. TdF-II (9 to 50 mu g/g mice) produced sialorrhea, dyspnea and death 1 hr after i.p. injection. Light microscopy of the pancreas revealed that TdF-III (3.42 mu g/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.