Lectins from Triticum vulgaris and Limax flavus are universal antagonists of botulinum neurotoxin and tetanus toxin.
Lectins from Anguilla anguilla, Artocarpus integrifolia, Canavalia ensiformis, Datora stramonium, Glycine max, Limax flavus, Ricinus communis and Triticum vulgaris were tested for their abilities to antagonize the binding of botulinum neurotoxin and tetanus toxin to rat brain membranes and to antagonize the ability of these toxins to block neuromuscular transmission in mouse phrenic nerve-hemidiaphragm preparations. Lectins from Limax flavus and Triticum vulgaris, both of which have affinity for sialic acid, were antagonists of the various serotypes of botulinum neurotoxin and tetanus toxin. When tested against the high affinity binding site for botulinum neurotoxin type B, the lectin from Limax flavus had a Ki of 3.1 x 10(-7) M and the lectin from Triticum vulgaris had a Ki of 3.75 x 10(-7) M. When tested against the high affinity binding site for tetanus toxin, the lectins from Limax flavus and Triticum vulgaris had Ki values of 1.5 x 10(-7) and 1 x 10(-6) M, respectively. In all cases the lectins behaved as competitive antagonists. In reverse experiments, neither botulinum toxin nor tetanus toxin was a very effective antagonist of lectin binding to brain membranes. Studies on isolated neuromuscular preparations showed that the lectin from Triticum vulgaris did not affect transmission at concentrations of 10(-6) to 10(-3) M, but at a concentration of 3 x 10(-5) M the lectin produced highly statistically significant antagonism of the neuromuscular blocking properties of botulinum neurotoxin types A, B, C, D, E and F as well as tetanus toxin. The lectin did not antagonize beta-bungarotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
Bakry
N
N
Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania.
Kamata
Y
Y
Simpson
L L
LL
D000818:Animals; D001904:Botulinum Antitoxin / Q000378:metabolism / Q000494:pharmacology; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D037121:Plant Lectins; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects; D013743:Tetanus Antitoxin / Q000378:metabolism / Q000494:pharmacology; D013744:Tetanus Toxin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000378:metabolism / Q000494:pharmacology*
D001904:Botulinum Antitoxin; D037102:Lectins; C042962:Limax flavus agglutinin; D009466:Neuromuscular Blocking Agents; D037121:Plant Lectins; D013743:Tetanus Antitoxin; D013744:Tetanus Toxin; D014909:Wheat Germ Agglutinins; D001905:Botulinum Toxins