Tetanus toxin attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C in NG-108 cells.
Although the pathology of tetanus toxin poisoning has been linked to an inhibition of neurotransmitter release, the mechanism of this inhibition is unknown. The neuroblastoma x glioma hybrid cell NG-108 is an emerging model in which to study the biochemical effect of tetanus toxin on acetylcholine secretion. In differentiated as well as undifferentiated NG-108 cells, a 4 hr tetanus toxin (10(-8) M) pretreatment had no effect on basal levels of cyclic AMP or cyclic GMP. In addition, toxin pretreatment did not affect agonist induced increases in either cyclic nucleotide. Treatment of NG-108 cells for 4 hr with 10(-10) M tetanus toxin had no effect on the subsequently measured activity of cytosolic protein kinase C. However, a 4 hr pretreatment of undifferentiated or differentiated cells with tetanus toxin (10(-8) or 10(-10) M respectively) significantly attenuated the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C. Direct addition of tetanus toxin (10(-7)-10(-10) M) to isolated protein kinase C did not alter the ability of the enzyme to phosphorylate histone protein. These results suggest that one manifestation of tetanus toxin poisoning may be a disruption in protein kinase C metabolism.
Considine
R V
RV
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Bielicki
J K
JK
Simpson
L L
LL
Sherwin
J R
JR
D000109:Acetylcholine / Q000378:metabolism; D000527:Alprostadil / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013744:Tetanus Toxin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013744:Tetanus Toxin; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D011493:Protein Kinase C; D000527:Alprostadil; D006152:Cyclic GMP; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate