Tetanus Toxin and Protein Kinase C

  • Robert V. Considine
  • Lance L. Simpson
  • Joseph R. Sherwin

Abstract

The pathogenesis of tetanus toxin poisoning is characterized by an inhibition of neurotransmitter release in the central nervous system; however, the exact mechanism through which the toxin inhibits exocytosis is not yet understood. A suitable neuronal model in which to study the biochemical effects of tetanus toxin on secretory processes is the differentiated neuroblastoma x glioma hybrid cell line NG-108.1 We have recently reported that tetanus toxin pretreatment of differentiated NG-108 cells attenuated the ability of phorbol myristate acetate (PMA) and neurotensin to mobilize cytosolic protein kinase C (PKC) to the plasma membrane.2,3 One implication of these observations is that the ability of tetanus toxin to alter PKC metabolism is related to its ability to inhibit exocytosis. In this study we have used a permeabilized cell/synthetic peptide assay to directly measure membrane PKC activity following tetanus toxin pretreatment. Further, we have used this assay to determine the efficacy of four putative inhibitors of membrane PKC activity; staurosporine and H-7 inhibit the catalytic site of the kinase, calphostin and sphingosine block the regulatory site. Finally, experiments were performed on neuromuscular preparations to test the hypotheses that PKC is required for short-term neuromuscular transmission and that the kinase could be the direct target of tetanus toxin.

Keywords

Phorbol Myristate Acetate Phorbol Myristate Acetate Tetanus Toxin Botulinum Neurotoxin Type Neuromuscular Preparation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Robert V. Considine
    • 1
  • Lance L. Simpson
    • 2
  • Joseph R. Sherwin
    • 1
  1. 1.Department of PhysiologyJefferson Medical CollegePhiladelphiaUSA
  2. 2.Departments of Medicine and PharmacologyJefferson Medical CollegePhiladelphiaUSA

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