Tetanus toxin inhibits neurotensin-induced mobilization of cytosolic protein kinase C activity in NG-108 cells.
There is considerable literature on the pathogenesis of tetanus toxin poisoning; however, the mechanism of action and intracellular substrate of this toxin have not been defined. It was demonstrated that the NG-108 neuroblastoma x glioma cell line is a suitable model in which to study the mechanism of tetanus toxin action, from binding of the toxin to inhibition of transmitter release. Further, it has been shown that tetanus toxin pretreatment attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C (PKC) in this cell line. In the present study a 4-hr tetanus toxin pretreatment (10(-10)-10(-13) M) completely inhibited the mobilization of cytosolic PKC induced by a 30-min exposure to 10 microM neurotensin. Pretreatment with 10(-10) M tetanus toxin for periods as short as 1 hr was sufficient to attenuate the ability of neurotensin to mobilize cytosolic PKC; however, a 30-min pretreatment had no significant effect. At a concentration of 10(-11) M, it was necessary to pretreat the cells for greater than 1 hr to significantly attenuate neurotensin-mobilized PKC activity. The exact role that PKC plays in the secretory process is not yet known; however, these findings suggest that the effect of tetanus toxin on neurotransmitter release is accompanied by an alteration in PKC metabolism in differentiated NG-108 cells.
Considine
R V
RV
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Handler
C M
CM
Simpson
L L
LL
Sherwin
J R
JR
D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D005910:Glioma / Q000201:enzymology; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology*; D009496:Neurotensin / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000378:metabolism*; D013744:Tetanus Toxin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D013744:Tetanus Toxin; D009496:Neurotensin; D011493:Protein Kinase C