Histamine Release by Calcium from Sodium Fluoride-Activated Rat Mast Cells. Further Evidence for a Secretory Process

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Abstract
Histamine release induced by calcium (step 2) from fluoride-activated (step 1) rat mast cells was found to be dependent on temperature and pH. Whereas the influence of temperature was different on the two steps, the pH effects were similar. The activation of the cells by fluoride occurred faster at low pH. Agents considered to influence cyclic nucleotide content of the cells neither influenced fluoride activation nor the secretory action of calcium, except for theophylline which inhibited the second step and shared this effect with lidocaine and several other agents known to act as inhibitors of histamine secretion. The time course for the action of fluoride to inhibit subsequent histamine release by compound 48/80 in the absence of extracellular calcium was somewhat faster than its action to activate the cells to the secretory action of calcium. In the absence of calcium, no cyclic AMP could be detected in the cells. In the presence of 1 mM calcium, 2.5 pmol/106 cells cyclic AMP was found which decreased by the presence of fluoride. No uptake of 45Ca was observed in fluoride-activated mast cells in the absence of release. Furthermore, fluoride did not activate isolated mast cell granules to release histamine when challenged with calcium. The results suggest that calcium-induced histamme secretion from fluoride-activated cells conforms to a secretory system which, in many respects, is governed by similar regulatory factors as for antigen and other secretagogues.