Effects of tetanus toxin on catecholamine release from intact and digitonin-permeabilized chromaffin cells.
Tetanus exotoxin inhibited Ca2+-dependent catecholamine secretion in a dose-dependent manner in digitonin-permeabilized chromaffin cells. The inhibition was specific for tetanus exotoxin and the B fragment of tetanus toxin; the C fragment had no effect. Inhibition required the introduction of toxin into the cell, and was not seen when intact cells were preincubated with the toxin or toxin fragments. The degree of inhibition was related to the length of preincubation with toxin, as well as the concentration of toxin used. A short preincubation with toxin was sufficient to inhibit secretion, and the continued presence of toxin in the incubation medium was not required during the incubation with Ca2+. The inhibition of secretion by tetanus toxin or the B fragment was not overcome with increasing Ca2+ concentrations. Tetanus toxin also inhibited catecholamine secretion enhanced by phorbol ester-induced activation of protein kinase C. Thus, the toxin or a proteolytic fragment of the toxin can enter digitonin-permeabilized cells to interact with a component of the Ca2+-dependent exocytotic pathway to inhibit secretion.
Bittner
M A
MA
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Holz
R W
RW
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002837:Chromaffin Granules / Q000187:drug effects* / Q000378:metabolism; D002838:Chromaffin System / Q000187:drug effects*; D004072:Digitonin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D010703:Phorbol Esters / Q000494:pharmacology; D013744:Tetanus Toxin / Q000494:pharmacology*; D013997:Time Factors
D002395:Catecholamines; D010703:Phorbol Esters; D013744:Tetanus Toxin; D001905:Botulinum Toxins; D004072:Digitonin; D002118:Calcium