Mechanism of Action of the Presynaptic Neurotoxin, Tetanus Toxin.
Abstract
The goal is to identify fundamental mechanisms involved in the action of the Clostridial neurotoxins, in particular tetanus toxin. A cultured cell line, PC12 cells, are very sensitive to tetanus toxin, i.e. the toxin inhibits depolarization evoked release of acetylcholine. This model cell system has been very valuable in the characterization of a binding-internalization-function process tor tetanus toxin. The toxin binds with nanomolar affinity and inhibits ACh release at doses as low as 0.1 nM. An important discovery is that we have found that analogues of cyclic guanosine monophosphate are capable of reversing the effects to tetanus toxin once they have have been established in these cells. This is important for two reasons: (1) the potential for development of therapeutic agents directed against Clostridial intoxication is very real; and (2) these results suggest that there is an important role for cGMP in the underlying mechanism of action of tetanus toxin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 30, 1987
- Accession Number
- ADA184817
Entities
People
- Terry B. Rogers
Organizations
- University of Maryland School of Medicine