The effect of alkaline earth cations on the release of histamine from rat peritoneal mast cells treated with compound 48/80 and peptide 401.

1 Extracellular calcium ions have a dual effect on the release of histamine from rat peritoneal mast cells treated with compound 48/80 and peptide 401. The release is either potentiated or inhibited according to the relative concentrations of ion and inducer.2 Strontium similarly potentiates the release produced by optimal concentrations of inducer but higher concentrations are required than in the case of calcium. Strontium is markedly less inhibitory than calcium.3 Mast cells may be depleted of intracellular calcium by incubation for short periods with the chelating agent, ethylenediamine tetraacetic acid (EDTA). They thereby become unresponsive to compound 48/80 and peptide 401 unless calcium is reintroduced into the incubation medium. Strontium and barium, but not magnesium, will substitute for calcium in this system. Barium additionally produces a marked release of histamine even in the absence of inducer. Pretreatment with the ionophore A23187 similarly inhibits the subsequent response to peptide 401 in divalent cation-free medium. This inhibition is reversed on the reintroduction of calcium.4 Compound 48/80 and peptide 401 release histamine from mast cells incubated in isotonic sucrose in the complete absence of added metal ions. However, the corrected release under these conditions is potentiated by both mono and divalent cations.5 On the basis of these results, the possible mechanism of action of the basic releasing agents and their usefulness as models for studying histamine secretion is discussed.