RT Journal Article SR Electronic T1 Suppression of Adenosine A3 Receptor-Mediated Hypotension and Mast Cell Degranulation in the Rat by Dexamethasone JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 725 OP 730 DO 10.1124/jpet.102.035790 VO 302 IS 2 A1 Jason P. Hannon A1 Bruno Tigani A1 Henk-Jan Schuurman A1 John R. Fozard YR 2002 UL http://jpet.aspetjournals.org/content/302/2/725.abstract AB Dexamethasone increases the expression of adenosine A3 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 A3 receptor stimulation in vivo. Administration of the A3 receptor agonist APNEA [N6-2-(4 aminophenyl)ethyladenosine; 10–30 μg 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 A1 receptor agonist N6-cyclopentyladenosine, the A2A receptor agonist 2-[p-(2-carboxyethyl)phenylamino]-5′-N-ethylcarboxamidoadenosine, or the mast cell degranulating agent compound 48/80 (100–300 μg kg−1, i.v.). APNEA (10 and 30 μg kg−1, i.v.) and compound 48/80 (100 and 300 μg 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 A3 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 A3 receptor, possibly at the level of the Gi family of trimeric GTP-binding proteins. The American Society for Pharmacology and Experimental Therapeutics