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The apomorphine-induced inhibition of histamine release in rat peritoneal mast cells was studied by means of secretagogues stimulating different pathways of mast cell activation. Apomorphine inhibited the mast cell response to all releasing agents (lysophosphatidylserine plus nerve growth factor, compound 48/80, substance P, ATP, tetradecanoylphorbolacetate, melittin). The IC50 ranged from 4 microM to 24 microM at concentrations of secretagogues releasing 30-50% of mast cell histamine. However, the potency of the drug decreased at higher secretagogue concentrations. Mast cells, pretreated with apomorphine and washed, released little histamine upon stimulation. The secretory response could be partially restored on increasing the concentration of secretagogues. The results suggest that apomorphine affects a regulatory step controlling the terminal sequence of mast cell secretory activity. As indicated by the reduced potency of the drug, the control by the apomorphine-sensitive reaction loses efficiency under conditions of massive histamine release.
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