HISTAMINE-RELEASE AND CALCIUM CONCENTRATIONS IN RAT MAST-CELLS ARE DEPENDENT ON INTRACELLULAR ATP - EFFECTS OF PROSTAGLANDIN D-2

When PGD(2) (10 mu M), was added to rat mast cells, it caused a rapid increase in adenosine 3',5'-cyclic monophosphate (cyclic AMP) and decr ease in adenosine 5'-triphosphate (ATP), both of which recovered to th eir original levels within 2 min. The accumulation of cyclic AMP was m aximal at 30 s after challenge with PGD(2). The minimum level of ATP w as observed at 30 s after addition of PGD(2). The initial rise in [Ca2 +](i) and the histamine release induced by anti-IgE (200 mu g/ml) were strongly inhibited at 30 s after incubation of the mast cells with PG D(2). Removal of glucose from Tyrode-Hepes solution caused a rapid dec rease on ATP level in mast cells, and showed strong inhibition on the rise in [Ca2+](i) and histamine release induced by anti-IgE. Addition of glucose to the mast cells induced a time-dependent increase in ATP, and the rises in [CA(2+)](i) and histamine release were closely corre lated with the recovery of ATP. These results suggested that the inhib itory mechanism of PGD(2) on the initial rise in [Ca2+](i) and histami ne release induced by anti-IgE was due to the inhibition of ATP-depend ent CA(2+)-release from the intracellular Ca2+-stores.