MODULATION OF CYCLIC-AMP IN PURIFIED RAT MAST-CELLS .3. STUDIES ON EFFECTS OF CONCANAVALIN A AND ANTI-IGE ON CYCLIC-AMP CONCENTRATIONS DURING HISTAMINE-RELEASE

Abstract

Changes in rat mast cell cyclic AMP (cAMP) concentrations during stimulation of histamine release by concanavalin A (con A) and anti-IgE were studied. Con A caused an increase in cAMP with a mean peak level at 20 s of 232% of control (range 165%-365%). Con A-stimulated cells demonstrated falls toward control levels after 20 s, but generally remained above control for at least 5 min. By 10 min cAMP had returned to control values. The con A effect on cAMP occurred in the absence of phosphatidyl serine but was markedly inhibited by 5 mM .alpha.-methyl-D-mannose. Anti-IgE [immunoglobulin E] induced a less marked increase in cAMP (157% of control, range 110%-540% of control) which reached a peak at 20 s. Two monospecific goat anti-rat myeloma IgE antisera induced similar changes in cAMP, whereas normal goat IgG had no effect. These peak values were followed by a rapid decrease in cAMP. Within 2 min the cAMP content of anti-IgE stimulated cells had fallen to levels well below control and remained below control levels from 45 s to over 15 min. Histamine release in both systems began after the peak cAMP levels, during the period of rapid destrucion of cAMP.