Mechanism of Action of the Presynaptic Neurotoxin, Tetanus Toxin
Abstract
Results obtained during this contract identify the metabolic pathway for cGMP as a potential site of action of tetanus toxin. Preliminary studies have revealed that guanylate cyclase activity is not inhibited in intoxicated PC12 cells. Although we can not rigorously rule out a possible role for this enzyme in toxin action, all of the evidence reported here is consistent with the view that the degradation of cGMP is stimulated in toxin-treated cells. The phosphodiesterase inhibitors, IBMX and zaprinast, were effective in reversing the effects of tetanus toxin on both the inhibition of evoked cGMP accumulation and ACh release in a similar manner. IBMX, a wide spectrum, rather low affinity, phosphodiesterase inhibitor, partially restored cGMP levels and ACh release. Zaprinast has been reported to be specific for cGMP degrading phosphodiesterases in a number of diverse tissues.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1991
- Accession Number
- ADA246780
Entities
People
- Terry B. Rogers
Organizations
- University of Maryland School of Medicine