RAT MAST-CELLS PERMEABILIZED WITH ATP SECRETE HISTAMINE IN RESPONSE TO CALCIUM-IONS BUFFERED IN THE MICROMOLAR RANGE

Rat mast cells treated with ATP (0.5-4 .mu.M) in the absence of divalent cations (so that almost all the ATP is present as ATP4-) became permeable to normally impermeant aqueous solutes, added extracellularly. These include the stable complexes Co HEDTA [hydroxyethyl-ethylene-diaminetriacetic acid] and Ca EDTA, and 6-carboxyfluorescein but not inulin. At 4 .mu.M-ATP4- the space accessible to Ca EDTA is 89% of that occupied by 3H2O. The kinetics of solute entry are regulated by the concentration of ATP4-. Ca2+, buffered in the range 1-10 .mu.M with HEDTA, causes histamine secretion from mast cell rendered permeable with ATP4-. The extent of secretion increases as the concentration of ATP4- is raised from 3 to 5 .mu.M. With extracellular Ca2+ present at physiological (millimolar) concentrations, the effect of increasing ATP4- through this range is to inhibit secretion. The rates of histamine secretion and of 32P-metabolite leakage from 32P-prelabelled cells in the presence of micromolar concentrations of Ca2+, were compared. The kinetics of both processes are regulated by the concentration of ATP4-, but not Ca2+.