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.

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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

Tags

DTIC Thesaurus Topics

  • Brain
  • Cell Line
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Contracts
  • Culture Techniques
  • Cultured Cells
  • Inhibition
  • Inhibitors
  • Medical Personnel
  • Metabolic Pathways
  • Neurons
  • Nucleotides
  • Tumor Cell Line

Fields of Study

  • Biology
  • Computer science

Readers

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