Dexamethasone increases the expression of
adenosine A(3) receptors and augments degranulation in response to their activation in the rat basophilic
leukemia cell line, RBL-2H3. We have studied the effects of
dexamethasone on mast cell activation induced by A(3) receptor stimulation in vivo. Administration of the A(3) receptor agonist
APNEA [N(6)-2-(4 aminophenyl)ethyladenosine; 10-30 microg kg(-1) i.v.] to anesthetized Sprague-Dawley rats induced falls in blood pressure. Pretreatment with
dexamethasone (1 mg kg(-1), i.p., -24 h) blocked the hypotensive response to
APNEA but not those induced by the A(1) receptor agonist
N(6)-cyclopentyladenosine, the A(2A) receptor agonist 2-[
p-(2-carboxyethyl)phenylamino]-
5'-N-ethylcarboxamidoadenosine, or the mast cell degranulating agent
compound 48/80 (100-300 microg kg(-1), i.v.).
APNEA (10 and 30 microg kg(-1), i.v.) and
compound 48/80 (100 and 300 microg kg(-1), i.v.) increased plasma
histamine concentrations dose dependently. Pretreatment with
dexamethasone significantly inhibited the increases induced by the lower doses of each compound.
APNEA induced degranulation of mast cells in thymus but not in skin or skeletal muscle, whereas
compound 48/80 induced degranulation in each tissue. Pretreatment with
dexamethasone inhibited
APNEA-induced degranulation of mast cells in the thymus and slightly, yet significantly, reduced degranulation induced by
compound 48/80. Thus, in contrast to the findings in RBL-2H3 cells in vitro, in the whole animal,
dexamethasone down-regulates the response of the mast cell to A(3) receptor activation. The qualitatively similar effects on
compound 48/80 suggest that
dexamethasone suppresses mast cell responsiveness by modulating site(s) downstream from the
adenosine A(3) receptor, possibly at the level of the G(i) family of trimeric
GTP-binding proteins.