Nedocromil sodium modulates the function of long-term rat peritoneal mast cell cultures

Long-term rat peritoneal mast cell (MC) cultures consisting of MC co-cultured with 3T3 fibroblasts (MC/3T3) were employed to study the effects of repeated and prolonged incubation with nedocromil sodium (10^-3 and 10^-5m) on MC activation. When nedocromil sodium was added simultaneously with compound48/80 to MC/3T3 on the first day of the experiment, it inhibited histamine release to the same extent as when added to the cultures a week later upon rechallenge. In other experiments activated MC/3T3 were incubated with nedocromil sodium for a week and on the last day of the experiment fresh nedocromil sodium was added simultaneously with compound48/80. Under these conditions the drug was as potent in inhibiting histamine release from the activated MC as it was in cultures incubated for a week with medium alone. In addition, preincubation of naive MC with nedocromil sodium for two days inhibited histamine release from these cells when activated for the first time. Salbutamol (10^-3 and 10^-5m) exhibited a similar inhibitory effect to nedocromil sodium upon simultaneous incubation with MC/3T3. However, prolonged incubation of salbutamol with MC/3T3 cultures resulted in tachyphylaxis. We conclude that nedocromil sodium is an effective MC stabilizing drug since it similarly inhibits histamine release from both primarily and secondarily challenged MC. Moreover this drug does not lose its efficacy upon prolonged incubation with MC.