Adenosine inhibits and potentiates IgE‐dependent histamine release from human basophils by an A2‐receptor mediated mechanism

Abstract

1 Adenosine added to human basophils before anti-IgE challenge inhibited histamine release, whereas addition after challenge potentiated release. Peak responses for the two effects occurred 15 min before and after challenge respectively. 2 The effects of adenosine on histamine secretion were dose-related over concentration ranges of 1–100 μm for inhibition and 0.01–1 μm for potentiation. 3 The capacity of adenosine to inhibit and potentiate histamine secretion was inversely related to the strength of immunological challenge. 4 The ability of theophylline (50 μm) to inhibit and dipyridamole (1 μm) to enhance slightly adenosine-induced responses, and the differing pharmacological effect of 2′,5′-dideoxyadenosine suggested that adenosine's effects on basophil histamine secretion were mediated by stimulation of cell surface adenosine receptors. 5 The order of potency of adenosine and its analogues l- and d- N⁶-phenylisopropyladenosine (PIA) and 5′-N-ethylcarboxamideadenosine (NECA) in inhibiting and potentiating IgE-dependent histamine release from basophils indicated that both responses were mediated by stimulation of the adenosine A₂-receptor subtype. 6 The capacity of adenosine to cause a transient increase of cyclic AMP levels in 40–70% basophil-enriched leucocytes confirmed the association between stimulation of A₂-receptors and activation of adenylate cyclase.