Native tetanus and pertussis toxins effect on electrical and chemical seizures in mice

摘要

The tetanus toxin (Tetx) administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) caused the death of 50% of experimental mice (LD50,) at a dose of 18.0 (11.5-28.2) MLDs or 11.0 (8.3-14.6) MLDs/kg each. The minimal lethal dose (MLD) is defined as the lowest dose of Tetx required to kill a 20.0 g albino mouse within 96 hours following i.p. treatment [24]. Tetx increased the convulsive threshold of the electrical current and diminished particular chemical convulsant potencies. At the same time Tetx increased the protection given by a number of anti-epileptics during maximal electroshock treatment (MES). There were no marked γ-aminobutyric acid (GABA) concentration and total L-glutamic acid decarboxylase activity changes(GAD) in whole-brain homogenates accompanying Tetx treatment. These results suggest the preponderance of inhibitory over excitatory transmission probably due to Tetx action at the neuronal level. Tetx that penetrates into the central nervous system (CNS) following an i.p. injection evokes changes similar to those noted during Tetx administration into the lateral ventricle. Thus, both routes of adminstration demonstrate comparable predictive values in describing Tetx-induced changes during convulsive thresholds. Pertussis toxins (0.5 μg/animal, i.c.v., 120 h prior to testing), enhanced the chemical convulsants potency and decreased the carbamazepine protection during MES. It remained without marked influence upon the action of diphenylhydantoin and diazepam. These observations suggest that the enhanced sensitivity towards a number of chemical convulsants, irrespective of their action possibly results from a functional suppression of the inhibitory transmission at receptors coupled with pertussis toxin sensitive G proteins, rather than due to direct action on the G protein linked excitatory neurotransmission. The attenuation of carbamazepine efficacy might result in the sum of adenosine receptor antagonist drug properties and transmission suppression at the level of adenosine receptors coupled with G proteins sensitive towards pertussis toxins. Both toxins did not influence the total plasma levels of any anti-epileptic drug. Thus, the observed interactions between Tetx/pertussis toxins and anti-epileptic drugs probably occur at the neuronal level.