Changes in cellular levels of cyclic AMP in rat mast cells during secretion of histamine induced by immunoglobulin E decapeptide and ACTH(1-24) peptide. Comparison with immunological and ionophore triggers.

The role of cyclic AMP in the secretory mechanism of mast cells has been investigated by comparing the time course of changes in cellular levels of this cyclic nucleotide with the kinetics of secretion induced by basic peptides, antigen, anti-IgE and calcium ionophore. ACTH(1-24) peptide and a synthetic decapeptide representative of the sequence 497-506 within the C epsilon 4 domain of human IgE induced a transient rise in cyclic AMP which reached approx. 150% of the resting levels by 10 s. Peptide-induced secretion of histamine was also rapid, reaching a maximum after 5-10 s. Immunological triggering of mast cells with antigen and anti-IgE raised levels of cyclic AMP to 150% of resting levels within 15 s, accompanying secretion of histamine which reached a maximum after 30 s. A relatively slower release of histamine induced by the calcium ionophore A23187 was paralleled by a significant reduction in cyclic AMP to 50% of the resting levels after 300 s. These data suggest a relationship between the accumulation of cyclic AMP in mast cells and secretion of histamine mediated by the C epsilon 4 decapeptide and the ACTH(1-24) peptide as well as by IgE-dependent mechanisms. However, the simultaneous increase in cyclic AMP and secretion of histamine suggests that the two events may not be causally related.