Adenylate cyclase, cyclic AMP and IgE-mediated desensitization in rat mast cells.

Rat peritoneal mast cells were desensitized up to 100% with 1-4 additions of suboptimal concentrations of anti-rat IgE over 60-90 min. Desensitized cells rechallenged with anti-IgE showed a 2- to 10-fold increase in cAMP during the initial 1-5 min. Membrane preparations from desensitized cells showed up to a 100-fold rise in cyclase activity following incubation with anti-IgE, compared to a 5- to 10-fold rise in control cells. Control and desensitized cell membranes rechallenged with anti-IgE showed nearly identical levels of phosphodiesterase activation. We conclude that following desensitization, repetitive low levels of anti-IgE binding induce atypically high and sustained activation of adenylate cyclase which may reflect primary or secondary regulatory events in the development of desensitization.