Accession Number : ADA184817

Title :   Mechanism of Action of the Presynaptic Neurotoxin, Tetanus Toxin.

Descriptive Note : Annual rept. 1 Apr 86-31 Mar 87,

Corporate Author : MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE

Personal Author(s) : Rogers, Terry B.

PDF Url : ADA184817

Report Date : 30 APR 1987

Pagination or Media Count : 34

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.

Descriptors :   *CLOSTRIDIUM, *TETANUS, *TOXINS AND ANTITOXINS, BACTERIAL TOXINS, PATHOGENESIS, CULTURES(BIOLOGY), ACETYLCHOLINE, FLUORESCENCE, NERVE TRANSMISSION, SYNAPSE, RAT, GUANOSINE, PHOSPHATES.

Subject Categories : Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE