INHIBITORY EFFECT OF ADENOSINE ON DEGRANULATION OF HUMAN CULTURED MAST-CELLS UPON CROSS-LINKING OF FC-EPSILON-RI

Adenosine is a potent bronchoconstricting agent that is released by ac tivated mast cells and hypoxic lung tissue, However, both inhibition a nd stimulation of mediator release from human lung mast cells by adeno sine have been described, and this discrepancy seems to be due to cont aminating cells or the effects of enzymatic treatment, We, therefore, investigated the effects of adenosine and its receptor-specific analog ues on human cultured mast cells (HCMC). Adenosine inhibited Fc epsilo n RI-mediated tryptase release from HCMC in a dose-dependent manner, a nd this inhibitory effect was completely blocked by the A2a receptor a ntagonist ZM241385. The specific agonist of A2a adenosine receptors CG S21680 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-de pendent manner and inhibited protein tyrosine phosphorylation includin g that of ERK-2, These results suggest that adenosine acts via A2 rece ptors to inhibit Fc epsilon RI-mediated mediator release from human ma st cells. (C) 1998 Academic Press.