Inhibition of histamine release from rat mast cells by botulinum C2 toxin

The effects of botulinum C2 toxin, which ADP-ribosylates actin, were studied on the stimulated histamine release of rat peritoneal mast cells. Treatment of mast cells with botulinum C2 toxin for 4 h inhibited histamine release stimulated by compound 48/80 or MCD-peptide maximally by about 50%. A half-maximal and maximal inhibition occurred at about 30 and 450 ng/ml botulinum C2 toxin. At similar concentrations the toxin ADP-ribosylated actin in intact mast cells. Botulinum C2 toxin largely impaired the histamine release stimulated by 12-O-tetradecanoylphorbol-13-acetate but not by the ionophore A23187. The data indicate that botulinum C2 toxin partially inhibits the stimulated histamine release and suggest that actin is involved in the stimulus-secretion coupling in mast cells.