title: Functional characterization of a basic D49 phospholipase A2 (LmTX-I) from the venom of the snake Lachesis muta muta (bushmaster).
abstract: The whole venom of Lachesis muta muta is preponderantly neurotoxic but moderately myotoxic on the chick biventer cervicis preparation (BCp). We have now examined these toxic activities of a basic phospholipase A(2), LmTX-I, isolated from the whole venom. LmTX-I caused a significant concentration-dependent neuromuscular blockade in the BCp. The time to produce 50% neuromuscular blockade was 14.7+/-0.75 min (30 microg/ml), 23.6+/-0.9 min (10 microg/ml), 34+/-1.7 min (2.5 microg/ml) and 39.2+/-3.6 min (1 microg/ml), (n=5/concentration; p<0.05). Complete blockade with all tested concentrations was not accompanied by inhibition of the response to ACh. At the highest concentration, LmTX-I (30 microg/ml) significantly reduced contractures elicited by exogenous KCl (20mM), increased the release of creatine kinase (1542.5+/-183.9 IU/L vs 442.7+/-39.8 IU/L for controls after 120 min, p<0.05), and induced the appearance of degenerating muscle fibers ( approximately 15%). Quantification of myonecrosis indicated 14.8+/-0.8 and 2.0+/-0.4%, with 30 and 10 microg/mlvenom concentration, respectively, against 1.07+/-0.4% for control preparations. The findings indicate that the basic PLA(2) present on venom from L. m. muta (LmTX-I) possesses a dominant neurotoxic action on isolated chick nerve-muscle preparations, whereas myotoxicity was mainly observed at the highest concentration used (30 microg/ml). These effects of LmTX-I closely reproduce the effects of the whole venom of L. m. muta in chick neuromuscular preparations.
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, Brazil.
authors.forename: Daniela C S
authors.initials: DC
authors.lastname: Damico
authors.forename: Lilian G F
authors.initials: LG
authors.lastname: Bueno
authors.forename: Léa
authors.initials: L
authors.lastname: Rodrigues-Simioni
authors.forename: Sérgio
authors.initials: S
authors.lastname: Marangoni
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz-Höfling
authors.forename: José Camillo
authors.initials: JC
authors.lastname: Novello
mesh_terms: D000109:Acetylcholine; D000818:Animals; D002645:Chickens; D003435:Crotalid Venoms / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009466:Neuromuscular Blocking Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010741:Phospholipases A / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D054467:Phospholipases A2; D011189:Potassium Chloride; D017819:Viperidae / Q000502:physiology*
chemical_list: D003435:Crotalid Venoms; C072644:Lachesis venom; D009466:Neuromuscular Blocking Agents; D011189:Potassium Chloride; D010741:Phospholipases A; D054467:Phospholipases A2; D000109:Acetylcholine