Mechanisms of the action of adenine on anti-allergic effects in mast cells.

INTRODUCTION: Mast cells play an important role in allergic responses. METHODS: We herein demonstrated the mechanisms of inhibitory effect of adenine on IgE/antigen-induced degranulation and TNF-α release in mast cells. RESULTS: We found that these effects were dependent on the amino group of adenine because purine only weakly inhibited degranulation. Adenine also inhibited Ca(2+) ionophore- and thapsigargin-induced degranulation, however, this inhibitory effect was weaker than that of the antigen. Therefore, the inhibitory effects of adenine on degranulation may be mediated before as well as after the Ca(2+) raise under the antigen stimulus. Adenine inhibited antigen-induced Syk and the subsequent induction of AKT and ERK activation under FcϵRI-mediated signal. Adenine also attenuated antigen-induced increase in Ca(2+) . Furthermore, adenine inhibited IgE/antigen-induced IKKα/β activation, which is involved in degranulation. Finally, adenine protected mice against anaphylactic allergic responses in vivo. CONCLUSIONS: The present study revealed a key role of adenine in the attenuation of allergic responses through the inhibition of Syk-mediated signal transduction and IKK-mediated degranulation.