Botulinum neurotoxin light chains inhibit both Ca(2+)-induced and GTP analogue-induced catecholamine release from permeabilised adrenal chromaffin cells.
Using digitonin-permeabilised bovine adrenal chromaffin cells, the effects of botulinum neurotoxin light chains on exocytosis triggered by Ca2+ or by GppNHp were examined. Botulinum neurotoxin D light chain, prepared as a His(6)-tagged recombinant protein, cleaved VAMP and substantially inhibited catecholamine release due to Ca2+ and GppNHp. Botulinum neurotoxin C1 and E light chains produced partial inhibition of both Ca(2+)- and GppNHp-induced catecholamine release. These results suggest that Ca(2+)-dependent exocytosis and Ca(2+)-independent exocytosis triggered by a non-hydrolysable GTP analogue occurs via a SNARE-dependent mechanism in chromaffin cells.
Glenn
D E
DE
Physiological Laboratory, University of Liverpool, UK.
Burgoyne
R D
RD
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003470:Culture Media; D006165:Guanylyl Imidodiphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D050600:SNARE Proteins; D015398:Signal Transduction; D033921:Vesicular Transport Proteins
D002395:Catecholamines; D003470:Culture Media; D008565:Membrane Proteins; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D006165:Guanylyl Imidodiphosphate; D001905:Botulinum Toxins; D002118:Calcium