On the mechanism of histamine release from sodium fluoride-activated mouse mast cells

We have found that sodium fluoride-induced histamine release from mouse mast cells occurs in two separate steps, activation in the presence of fluoride and absence of calcium, and secretion triggered by calcium. The amount of released histamine was dependent either on the time of cell exposure to fluoride or on the final fluoride concentration in the incubation medium. The secretory step depends on the concentration of extracellular calcium; it increased as the concentration of calcium was increased. However, a substantial part of the release was both calcium and energy independent. This part, probably cytotoxic, increased markedly at the highest concentration and with extended times of cell exposure to fluoride. Among other divalent cations tested only strontium could partly substitute calcium to trigger secretion. The activating action of fluoride slowly decayed with time and addition of calcium for up to 2 h caused histamine release. Both steps were dependent on temperature and pH and were inhibited by antimycin A, suggesting that the reaction was enzymatic. The action of fluoride on mouse mast cells closely resembles its action on rat mast cells; however, some differences were also observed.