title: Reductive chain separation of botulinum A toxin--a prerequisite to its inhibitory action on exocytosis in chromaffin cells.
abstract: Cleavage of the disulfide bond linking the heavy and the light chains of tetanus toxin is necessary for its inhibitory action on exocytotic release of catecholamines from permeabilized chromaffin cells [(1989) FEBS Lett. 242, 245-248; (1989) J. Neurochem., in press]. The related botulinum A toxin also consists of a heavy and a light chain linked by a disulfide bond. The actions of both neurotoxins on exocytosis were presently compared using streptolysin O-permeabilized bovine adrenal chromaffin cells. Botulinum A toxin inhibited Ca2+-stimulated catecholamine release from these cells. Addition of dithiothreitol lowered the effective doses to values below 5 nM. Under the same conditions, the effective doses of tetanus toxin were decreased by a factor of five. This indicates that the interchain S-S bond of botulinum A toxin must also be split before the neurotoxin can exert its effect on exocytosis.
authors.affiliation: Abteilung Anatomie und Zellbiologie, Universität Ulm, FRG.
authors.forename: B
authors.initials: B
authors.lastname: Stecher
authors.forename: M
authors.initials: M
authors.lastname: Gratzl
authors.forename: G
authors.initials: G
authors.lastname: Ahnert-Hilger
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001905:Botulinum Toxins / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects; D004220:Disulfides / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*
chemical_list: D002395:Catecholamines; D004220:Disulfides; D001905:Botulinum Toxins; D002118:Calcium; D004229:Dithiothreitol