Botulinum A neurotoxin unlike tetanus toxin acts via a neuraminidase sensitive structure.
The binding and effects of tetanus and botulinum A neurotoxins were studied on mouse spinal cord cultures treated with neuraminidase. In untreated cultures both neurotoxins blocked synaptic transmission. Treatment of the cell cultures with neuraminidase, 25 mU/ml for 24 hr, decreased the potency of botulinum A neurotoxin. At 7 X 10(-11) M no toxin effect on inhibitory or excitatory synapses was observed, whereas at higher concentrations of the toxin the concentration-response curve was shifted to the right by a factor of about 30. Surprisingly, the action of tetanus toxin over a large concentration range was unaffected by pretreatment of the neurones with the enzyme. Accordingly, neurones treated with neuraminidase failed to bind 125I-botulinum A neurotoxin, whereas labelled tetanus toxin was still fixed by cell bodies, as well as by neurites, as shown by histoautoradiography. Chromatographic extraction of gangliosides from cultures prelabelled with 14C-glucosamine showed a dramatic loss in the contents of polysialogangliosides following treatment with neuraminidase. Our results indicate that neuraminidase-sensitive structures might be important for the action of botulinum A neurotoxin. The effect of tetanus toxin appears to be mediated by a different site which is insensitive to neuraminidase.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001665:Binding Sites; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D046508:Culture Techniques; D005732:Gangliosides / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009439:Neuraminidase; D009474:Neurons / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000378:metabolism; D013569:Synapses / Q000187:drug effects; D013744:Tetanus Toxin / Q000378:metabolism / Q000494:pharmacology
D005732:Gangliosides; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D013744:Tetanus Toxin; C028728:tetanus toxin receptor; D009439:Neuraminidase; D001905:Botulinum Toxins