Modulation of histamine release from human basophils and mast cells by adenosine

Immunological activation of human basophils was associated with a transient monophasic rise in the cellular cyclic AMP content, which precedes the onset of mediator release. However, in the same cell preparations non-immunological secretagogues produced similar degrees of histamine release without producing large changes in the cellular cyclic AMP content. The inconsistent relationships between histamine release and cyclic AMP production suggest that cyclic AMP changes are not a key event in the secretory proces. Additionally, in human basophils immunological activation was not associated with a marked increase in phospholipid methylation, therefore questioning the importance of this biochemical event to the secretory process. In human basophils and lung mast cells when added before immunological challenge adenosine inhibited histamine secretion and when added after challenge potentiated mediator release. Both effects appear to be mediated by stimulation of A2 purinoceptors. Additionally, adenosine and analogues which act at intracellular P-sites also inhibit immunologically and non-immunologically stimulated histamine secretion. These observations provide circumstantial evidence for a role for cyclic AMP in controlling mediator secretion. In rat mast cells adenosine enhanced immunologically stimulated mediator release. This effect was produced by the interaction of the neucleoside with a cell surface purinoceptor which could not be readily classified into the A1/A2 subtypes of purinoceptor. The enhancement of mediator release was associated with a prolongation of the cyclic AMP response of the cells to immunological stimulation. However, purinoceptor antagonists had no effect on the adenosine mediated enhancement of mediator secretion but did abrogate the effect on cyclic AMP, suggesting that the two events were unrelated. The mechanisms by which adenosine and its analogues may modulate mediator secretion from rat mast cells, human mast cells and basophils are discussed. (D68303/86)