title: Reciprocal modulation of anti-IgE induced histamine release from human mast cells by A₁ and A(2B) adenosine receptors.
abstract: OBJECTIVE
  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 (A₁, A(2A) , A(2B) and A₃) in primary human cultured mast cells (HCMC).
  
  
  METHODS
  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.
  
  
  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 A₁ AR agonists CCPA and 2'MeCCPA, and inhibited by the A₁ AR antagonist PSB36. In contrast, the inhibitory action of adenosine was mimicked by the non-specific A₂ 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
  We have defined for the first time the contribution of A₁ 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 A₁ AR antagonists, but not A(2B) AR antagonists.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: K H
authors.initials: KH
authors.lastname: Yip
authors.forename: H Y A
authors.initials: HY
authors.lastname: Lau
authors.forename: H
authors.initials: H
authors.lastname: Wise
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D002478:Cells, Cultured; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043683:Receptors, Adenosine A2 / Q000378:metabolism*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; C026408:anti-IgE antibodies; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine