Inhibitory Effect of Adenosine on Degranulation of Human Cultured Mast Cells upon Cross-linking of FcϵRI

Abstract

Adenosine is a potent bronchoconstricting agent that is released by activated mast cells and hypoxic lung tissue. However, both inhibition and stimulation of mediator release from human lung mast cells by adenosine have been described, and this discrepancy seems to be due to contaminating cells or the effects of enzymatic treatment. We, therefore, investigated the effects of adenosine and its receptor-specific analogues on human cultured mast cells (HCMC). Adenosine inhibited FcϵRI-mediated tryptase release from HCMC in a dose-dependent manner, and this inhibitory effect was completely blocked by the A2a receptor antagonist ZM241385. The specific agonist of A2a adenosine receptors CGS21680 inhibited the release of tryptase more potently than A1 and A3 agonists, and A2a receptor mRNA was detected by RT-PCR, suggesting the involvement of A2a receptors in the inhibitory effects of adenosine. In addition, adenosine increased intracellular cAMP level in a dose-dependent manner and inhibited protein tyrosine phosphorylation including that of ERK-2. These results suggest that adenosine acts via A2 receptors to inhibit FcϵRI-mediated mediator release from human mast cells.