Rat peritoneal mast cells have been used to study further the effect of drugs on the calcium-independent and calcium-dependent stages of phospholipase-A-induced mast cell degranulation. Evidence is presented which suggests that disodium cromoglycate (DSCG) and drugs known to raise the level of intracellular cyclic AMP block the degranulation process during, or after, the calcium-dependent step. The cyclic AMP active drugs and DSCG also potently inhibited calcium-independent compound 48/80-induced degranulation. In contrast diisopropylfluorophosphate (DFP), which potently inhibited antigen-induced mast cell degranulation, completely failed to inhibit either calcium-independent 48/80- or calcium-independent noradrenaline-induced degranulation. It is concluded that the DFP-sensitive step in the process of antigen-induced mast cell degranulation is independent of the cyclic nucleotide system and that the therapeutic effect of DSCG does not involve the DFP-sensitive step.

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