Effect of cromolyn sodium and deuterium oxide on anaphylactic histamine release from rat peritoneal mast cells in vitro.

Previous studies had shown that cromolyn sodium would inhibit anaphylactic histamine release from rat peritoneal mast cells in vitro (J. Pharmacol. Exp. Ther. 184: 41, 1973), under conditions where the maximum release was usually less than 30% of the total. In this report, deuterium oxide (D2O) is shown to potentiate anaphylactic histamine release from rat peritoneal mast cells in vitro. The cells were sensitized in vitro with rat reaginic antiovalbumin and challenged in vitro. The histamine was measured fluorometrically. At 37 degrees C the effect of D2O was concentration dependent with a 1.3-fold potentiation at 5% (v/v) and a 3-fold potentiation at 25% D2O (v/v). There was no effect of these levels of D2O on spontaneous histamine release. To be able to measure the rate of release, the sensitized cells were challenged with antigen at 25 degrees C in the presence and absence of D2O. Under these conditions, D2O increased both the rate of release and the total amount of release proportionately so that the T1/2 of release was not affected by D2O. The concentration of cromolyn sodium necessary to obtain 50% inhibition of histamine release increased from 6 muM in 0% D2O, to 80 muM in 10% D2O and to greater than 500 muM in 25% D2O. However, the lines showing the relationship between cromolyn sodium concentration and percent histamine released were not shifted in a parallel manner by D2O. This suggests that the interaction between D2O, cromolyn sodium and the histamine-releasing processes of mast cells is not a simple one.