Central Nervous Effects of the Convulsant Protein Canatoxin *

Abstract

12hsiraci: Some pharmacological-toxicological effects of canatoxin, a toxic protein purified from the seeds of Canavalia ensiforrnis have been studied in mice and rats. The most obvious effect, a lethal tonic convulsion, was generally produced 10-15 rnin. after intravenous injection of 2-3 mg/kg of the highly purified protein (mol. wt. 88,000). After intraperitoneal, intramuscular or subcutaneous administration the convulsion produced by the same toxin dosis occurred within 24 hours. A spinal transection at the midthoracic level did not abolish the convulsions of the hindlimbs while destruction of the medulla below this level completely blocked the convulsions of the hindlimbs. The convulsions of the head and forelimbs were unaffected by these surgical pretreatments. The toxic protein did neither affect the isolated skeletal muscle nor did it potentiate nerve impulse induced contractions. The convulsive effect of canatoxin was potentiated by reserpine and attenuated by phenobarbital, diazepam, methenesine and also by haloperidol and spiroperidol. The total concentration of brain and spinal cord neurotransmitters seemed to remain unchanged after subconvulsive and convulsive doses of canatoxin. In the conscious rat the toxic protein did not change the blood pressure except for a shortlasting hypertensive response observed immediately before the onset of the convulsions. The heart frequency was lowered at subconvulsive and convulsive dosis but no effect was seen on the frequency of the rat isolated right atria exposed to high doses of canatoxin. The body temperature was lowered by a convulsive dosis of the toxic protein. The purified toxin did not show any haemagglutinating property or haemolytic phospholipase A2-like activity. The results strongly suggest a central nervous site for the action ofcanatoxin. However, if the effects are produced by the intact protein or not as well as its exact mode of action, remain unexplained.

Jaburetox-2Ec: An insecticidal peptide derived from an isoform of urease from the plant Canavalia ensiformis

“…This internal sequence is also not responsible for the toxicity of canatoxin as Jaburetox-2Ec was innocuous at a 20fold higher protein mass/body weight ratio than the LD 50 for mice and rats [5,8], either by intraperitoneal injection or by oral route (neonatal rats were chosen because of the increased permeability of their digestive tract).…”

“…Mice and neonate rats injected with a single dose of 10 mg/kg of Jaburetox-2Ec were alive and showed no signs of toxicity 5 days after the injection, contrasting to animals that received intraperitoneally 3 mg/kg of canatoxin (equivalent to 1.5 LD 50 [13]), which died within 12 h after injection. The toxic effects of canatoxin in mice and rats have been previously described [5,8]. When Jaburetox-2Ec or canatoxin were given by oral route at the same dose, all animals survived with no symptoms of intoxication.…”

Ureases: Historical aspects, catalytic, and non-catalytic properties – A review

“…The ability of CNTX to promote secretion in synaptosomes correlates with the neurotoxicity it induces in vivo in mice and rats. The medullar origin of CNTX-induced seizures and other CNS-related effects were described in rodents [159] .…”

Toxic proteins in plants

“…Toxic symptoms provoked by canatoxin include respiratory distress and tonic convulsions of spinal cord origin, ultimately leading to the death of the animal. The central nervous system was identified as one of the target organs for canatoxin and certain neurotransmitters can be released dose-and time-dependently after incubation with canatoxin (Carlini et al, 1984). According to experiments using sarcoplasmic reticulum vesicles, canatoxin was deemed to disrupt the Ca 2+ transport by the Ca 2+ ATPase, leading to an increased cytoplasmic Ca 2+ concentration, which eventually triggers exocytosis (Alves et al, 1992).…”