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Differential expression and signaling of adenosine receptors in mouse bone marrow neutrophils
Author(s) -
Hoeven Dharini,
Auchampach John A.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.729.5
Subject(s) - agonist , adenosine , chemistry , adenosine receptor , chemokine , receptor , signal transduction , chemotaxis , inflammation , adenosine a3 receptor , purinergic signalling , bone marrow , intracellular , medicine , endocrinology , pharmacology , microbiology and biotechnology , biology , biochemistry
Adenosine suppresses neutrophil activity at sites of inflammation. Most inhibitory effects of adenosine on neutrophil function have been attributed to the A 2A AR, although recently we discovered that the A 3 AR also plays a role. Goals of this study were to determine if exposure to inflammatory stimuli regulates A 3 AR expression in mouse bone marrow neutrophils (BMNs), and to explore the signaling mechanisms by which the A 3 AR inhibits neutrophil function. Real time RT‐PCR and radioligand binding analyses revealed that expression of the A 2A AR but not the A 3 AR was increased ~10‐fold in BMNs obtained from LPS‐treated mice compared to controls. Despite selective induction of the A 2A AR in BMNs from LPS‐treated mice, potencies of both the A 2A AR‐selective agonist CGS 21680 and the A 3 AR‐selective agonist CP‐532,903 to inhibit fMLP‐induced superoxide production were increased compared to naïve BMNs. Mechanistic studies using naïve BMNs determined that activation of the A 3 AR inhibits BMN functions neither by increasing intracellular cAMP, nor by cross‐desensitizing chemoattractant or ATP receptors. We conclude that, unlike the A 2A AR, A 3 AR expression is not induced during inflammation. In addition, we conclude that A 3 AR activation inhibits BMN function by a signaling mechanism that is distinctly different from the A 2A AR. Supported by NIH Grants RO1 HL 077707, RO1 HL 60051 and by AHA Predoctoral Fellowship 0615533Z