Antibodies against rat brain vesicle-associated membrane protein (synaptobrevin) prevent inhibition of acetylcholine release by tetanus toxin or botulinum neurotoxin type B.
Tetanus and botulinum B neurotoxins are zinc endopeptidases that cleave vesicle-associated membrane protein (VAMP or synaptobrevin) at a single peptide bond. To test the possibility that in vivo also the toxin-induced blockade of neurotransmission is due to cleavage of VAMP, rat brain VAMP-specific antibodies were raised in rabbits. IgGs purified from one antiserum, which bind specifically to rat brain VAMP, also specifically recognize proteins from Aplysia californica in immunoblotting. When injected into neurons in the buccal ganglion of Aplysia, these IgGs did not affect the release of acetylcholine but effectively prevented the inhibitory action of both toxins on neurotransmitter release, thus indicating that the block of neurotransmission by these neurotoxins is consequent to the cleavage of VAMP or specific interaction with VAMP.
Poulain
B
B
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif-sur-Yvette, France.
Rossetto
O
O
Deloye
F
F
Schiavo
G
G
Tauc
L
L
Montecucco
C
C
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001048:Aplysia; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007267:Injections; D007425:Intracellular Membranes; D008565:Membrane Proteins / Q000276:immunology*; D008666:Metalloendopeptidases / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009474:Neurons / Q000187:drug effects; D050683:R-SNARE Proteins; D011817:Rabbits; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects; D013744:Tetanus Toxin / Q000494:pharmacology
D000906:Antibodies; D007074:Immunoglobulin G; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D013744:Tetanus Toxin; D008666:Metalloendopeptidases; C093556:zinc-endopeptidase, tetanus neurotoxin; D001905:Botulinum Toxins; D000109:Acetylcholine