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Reciprocal modulation of anti‐IgE induced histamine release from human mast cells by A 1 and A 2B adenosine receptors
Author(s) -
Yip KH,
Lau HYA,
Wise H
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01446.x
Subject(s) - adenosine , histamine , mast cell , adenosine receptor , chemistry , agonist , pharmacology , medicine , adenosine a2b receptor , endocrinology , immunoglobulin e , receptor , degranulation , biology , biochemistry , immunology , antibody
BACKGROUND AND PURPOSE Adenosine is believed to participate in the pathological development of asthma through a mast cell‐dependent mechanism. Our study aimed to pharmacologically characterize the functions of adenosine receptor (AR) subtypes (A 1 , A 2A , A 2B and A 3 ) in primary human cultured mast cells (HCMC). EXPERIMENTAL APPROACH HCMC were derived from progenitor stem cells in buffy coat and the effects of adenosine receptor ligands on basal and IgE‐dependent histamine release were evaluated. KEY RESULTS Adenosine and analogues alone did not induce HCMC degranulation. When HCMC were activated by anti‐IgE after 10 min pre‐incubation with adenosine, a biphasic effect on histamine release was observed with enhancement of HCMC activation at low concentrations of adenosine (10 −9 –10 −7 mol·L −1 ) and inhibition at higher concentrations (10 −6 –10 −4 mol·L −1 ). The potentiating action was mimicked by A 1 AR agonists CCPA and 2'MeCCPA, and inhibited by the A 1 AR antagonist PSB36. In contrast, the inhibitory action of adenosine was mimicked by the non‐specific A 2 AR agonist CV1808 and attenuated by A 2B AR antagonists PSB1115 and MRS1760. The non‐selective AR antagonist CGS15943 attenuated both the potentiating and inhibitory actions. CONCLUSIONS AND IMPLICATIONS We have defined for the first time the contribution of A 1 and A 2B ARs, respectively, to the potentiating and inhibitory action of adenosine on human mast cell activation. With reference to the current trend of developing novel anti‐asthmatic agents from AR ligands, our results suggest that inhibition of human mast cell activation would be a mechanism for A 1 AR antagonists, but not A 2B AR antagonists.