Mechanism of Action of the Presynaptic Neurotoxin: Tetanus Toxin
Abstract
The main goal of this study has been to identify the mechanism of action of the potent neurotoxins produced by the bacteria of the Clostridial strain. We have utilized tetanus toxin as a model system and have examined its action on the the inhibition of neurotransmitter release in a cloned neural cell line, PC12. Considerable information has been obtained indicating that tetanus toxin interferes with cyclic GMP metabolism in neural cells and that this process is crucial in the intoxication pathway. First, tetanus toxin infection results in inhibition of cyclic GMP accumulation in PC12 cells. The time course for the onset of the inhibition of neurosecretion and cyclic GMP increase were identical. Further, inhibitors of phosphodiesterase restore cGMP levels and neurotransmitter release in a parallel fashion. This result provides the first evidence that the effects of Clostridial infections can be reversed by pharmacological methods. These studies have been expanded to examine the effects of tetanus toxin and cGMP in a preparation of permeabilized PC12 cells. Using this system we have found that tetanus toxin alters the sensitivity of neurotransmitter release to Ca2+. Further, a cGMP stimulates secretion in these permeabilized cells. Future work will focus on the site of action of tetanus toxin in the cGMP metabolic pathway, particularly on phosphodiesterases in neural cells. Keywords: Tetanus toxin; Presynaptic toxin; Membrane models; Biotechnology; BD; Neurotoxins; Pretreatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 30, 1989
- Accession Number
- ADA210187
Entities
People
- Terry B. Rogers
Organizations
- University of Maryland School of Medicine