Mast cell desensitization to IgE fails to induce a parallel adenosine receptor desensitization.

Desensitization induced by challenge of mast cells with antigen is specific for IgE-dependent signals. During the secretory process mast cells release adenosine, which can induce a desensitization of adenosine receptors. To determine whether adenosine receptors may be desensitized from a previous antigen challenge, mast cells were sensitized with anti-DNP IgE antibody, challenged with DNP-BSA antigen, returned to culture overnight, resensitized, and rechallenged. Previously challenged cells exhibited increased spontaneous beta-hexosaminidase release, but adenosine retained its ability to augment beta-hexosaminidase release. Adenosine enhanced A23187-stimulated release of beta-hexosaminidase in control and previously challenged cells. Leukotriene C4 generation followed a similar pattern. Mastoparan, a direct G protein activator and mast cells secretagogue, produced a doubling of beta-hexosaminidase release in previously challenged cells. Results using other G protein activators were equivocal. Degranulation alone is insufficient to induce adenosine receptor hyposensitization. Whether the hyperresponsiveness to mastoparan is a consequence of uncoupling of IgE receptors from G proteins remains uncertain.