Regulation of IgE receptor-mediated secretion from RBL-2H3 mast cells by GTP binding-proteins and calcium

Abstract In RBL-2H3 rat basophilic leukemia cells, cholera toxin does not per se stimulate secretion but it enhances secretion stimulated by antigens that crosslink IgE receptors, by the Ca 2+ ionophore, ionomycin, and by thapsigargin, a tumor promoter that releases cytoplasmic Ca 2+ stores. Calmodulin inhibitors reduce both the basal and cholera toxin-enhanced secretory responses to antigen and Ca 2+ -mobilizing agents. These synergistic effects suggest that the activation of a G s -like GTP-binding protein, together with a (probably calmodulin-dependent) event activated by an increase in cytoplasmic Ca 2+ levels, may jointly provide a sufficient signal for secretion. Antigen-stimulated secretion is inhibited by depleting cells of GTP with mycophenolic acid but is maximal in cells treated with mycophenolic acid plus cholera toxin. The simplest explanation is that cholera toxin selectively reactivates the G s -coupled pathway leading to secretion in GTP-depleted cells without restoring the activity of a separate GTP-binding protein(s) that constrains antigen-stimulated secretion.