DEXAMETHASONE UP-REGULATES A(3) ADENOSINE RECEPTORS IN RAT BASOPHILICLEUKEMIA (RBL-2H3) CELLS

The cross-linking of surface IgE receptors by multi-functional Ags pro motes the degranulation of mast cells. Previous studies have indicated that the nucleoside adenosine potentiates this response by activating putative A(3) adenosine receptors (AR) coupled to phospholipase C in mast cells or their cultured analogues, rat basophilic leukemia (RBL-2 H3) cells. Moreover, it has been shown that exposure of RBL-2H3 cells to dexamethasone attenuated antigen-mediated mast cell degranulation, but potentiated the response elicited by adenosine. To determine wheth er the A(3)AR is a potential site of action of dexamethasone, we have assessed the status of these receptors in RBL-2H3 cells treated with a nd without dexamethasone. Treatment with dexamethasone (100 nM) for 24 h resulted in an increase in the number of A(3)AR to 217 +/- 50% of c ontrol. The increased receptor expression was both time- and concentra tion-dependent, with optimal increases observed following 16 h of trea tment and using 100 nM of dexamethasone. No increase in the level of t he A(2a)AR was detectable following dexamethasone treatment. Northern blotting studies indicated a 2.7 +/- 0.3-fold increase in A(3)AR mRNA in RBL-2H3 cells treated with dexamethasone for 24 h. Dexamethasone al so increased the expression of G protein alpha(i2), alpha(i3), alpha(s ), and beta subunits by two- to threefold. Activation of the A(3)AR by aminophenylethyladenosine (APNEA) following dexamethasone treatment e nhanced the production of inositol phosphates and the mobilization of intracellular Ca2+ From these data, it is concluded that dexamethasone increases the expression of both A(3)AR and G proteins in RBL-2H3 cel ls which contributes to the enhanced response to adenosine.