ISSN:
1432-1912
Keywords:
α-Toxin
;
Proteinkinase C
;
Exocytosis
;
G-Proteins
;
Cyclic nucleotides
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Tetanus and botulinum A neurotoxins inhibited exocytosis evolved by various secretagogues in intact and permeabilized chromaffin cells. The block of exocytosis in intact chromaffm cells due to botulinum A neurotoxin could partially be overcome by enhancing nicotine- and veratridine-induced stimulation, whereas the block due to tetanus toxin persisted under the same conditions. The receptor-mediated restoration of 3H-noradrenaline release was specific for nicotinic stimulation, because exocytosis did not occur during muscarinic stimulation. Depolarization of intact chromaffin cells with increasing concentration of K+ failed to restore exocytosis that had been blocked by either toxin. When chromaffin cells, treated with tetanus or botulinum A neurotoxins, were exposed to the Ca2+-ionophore A 23187 or permeabilized by staphylococcal α-toxin, Ca2+-stimulated exocytosis was also inhibited. The inhibition was unaffected by increasing concentrations of free Ca2+. Activation of proteinkinase C and of G-proteins by phorbolester and GMPPNHP, respectively, increased Ca2+-induced exocytosis in control cells as well as in cells treated with tetanus and botulinum A neurotoxins. The block, however, could not be relieved by these manipulations, and it could not be relieved by activating the cGMP or cAMP pathways with analoga of cyclic nucleotides, phosphodiesterases inhibitors, and forskolin either. It is concluded that nicotine and veratridine trigger a mechanism within the sequence of events leading to exocytosis that is located beyond the increase in intracellular Ca2+-concentration. This pathway may not be affected by botulinum A neurotoxin. The target of tetanus toxin is probably located even closer to the fusion process, i. e. beyond the step upon which botulinum A neurotoxin acts.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00172577
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