Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action.
Tetanus toxin (100 nM) when preincubated with guinea pig cerebrocortical synaptosomes for 45 min reduces the final extent of the KCl-evoked, Ca(2+)-dependent, glutamate transmitter release to 30% of non-intoxicated controls. Similarly, 100 nM Botulinum neurotoxins, types A and B, preincubated for 90 min inhibit release to 45-60% of non-intoxicated controls. The toxins preferentially attenuate a slow phase of KCl-evoked glutamate release which may be associated with synaptic vesicle mobilization. Tetanus toxin additionally inhibits the release of aspartate, gamma-aminobutyric acid and met-enkephalin from the same preparation. Since amino acids and neuropeptides are released by distinct mechanisms, this indicates that the toxin affects a step common to both exocytotic pathways. When Ba2+ (which does not interact with calmodulin) is substituted for Ca2+, the control KCl-evoked release of each transmitter is unaffected and tetanus toxin is still inhibitory. Taken together these results implicate a calmodulin-independent locus (or loci) of action common to small- and large-dense-core vesicles and associated with vesicle transport.
McMahon
H T
HT
Department of Biochemistry, University of Dundee, United Kingdom.
Foran
P
P
Dolly
J O
JO
Verhage
M
M
Wiegant
V M
VM
Nicholls
D G
DG
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001464:Barium / Q000378:metabolism; D001905:Botulinum Toxins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006168:Guinea Pigs; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013744:Tetanus Toxin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D013744:Tetanus Toxin; D001464:Barium; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; D001905:Botulinum Toxins; D002118:Calcium