Article

Suppression of adenosine A(3) receptor-mediated hypotension and mast cell degranulation in the rat by dexamethasone.

Research Department, Novartis Pharma AG, CH-4002 Basel, Switzerland.
Journal of Pharmacology and Experimental Therapeutics (impact factor: 3.83). 09/2002; 302(2):725-30. DOI:10.1124/jpet.102.035790
Source: PubMed

ABSTRACT 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.

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    American Journal of Respiratory Cell and Molecular Biology 06/2011; 45(6):1222-31. · 5.13 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

anesthetized Sprague-Dawley rats induced
 
APNEA induced degranulation
 
augments degranulation
 
compound 48/80 induced degranulation
 
degranulation induced
 
dexamethasone inhibited APNEA-induced degranulation
 
dexamethasone suppresses mast cell responsiveness
 
hypotensive response
 
increases induced
 
mast cell
 
mast cell activation induced
 
mast cell degranulating agent compound 48/80
 
mast cells
 
modulating site(s)
 
plasma histamine concentrations dose dependently
 
qualitatively similar effects
 
rat basophilic leukemia cell line
 
RBL-2H3 cells
 
skeletal muscle
 
trimeric GTP-binding proteins