Regulation of IgE receptor-mediated secretion from RBL-2H3 mast cells by GTP binding-proteins and calcium.
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 Ca2+ ionophore, ionomycin, and by thapsigargin, a tumor promoter that releases cytoplasmic Ca2+ stores. Calmodulin inhibitors reduce both the basal and cholera toxin-enhanced secretory responses to antigen and Ca2(+)-mobilizing agents. These synergistic effects suggest that the activation of a Gs-like GTP-binding protein, together with a (probably calmodulin-dependent) event activated by an increase in cytoplasmic Ca2+ 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 Gs-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.
Wilson
B S
BS
Department of Pathology, University of New Mexico, Albuquerque 87131.
Deanin
G G
GG
Oliver
J M
JM
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007073:Immunoglobulin E / Q000276:immunology; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D007942:Leukemia, Experimental; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D009173:Mycophenolic Acid / Q000494:pharmacology; D051381:Rats; D011961:Receptors, Fc / Q000187:drug effects / Q000502:physiology*; D017455:Receptors, IgE; D012701:Serotonin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014268:Trifluoperazine / Q000494:pharmacology
D000944:Antigens, Differentiation, B-Lymphocyte; D002147:Calmodulin; D011961:Receptors, Fc; D017455:Receptors, IgE; D013449:Sulfonamides; D013729:Terpenes; D014268:Trifluoperazine; D012701:Serotonin; D007073:Immunoglobulin E; C017967:W 7; D019284:Thapsigargin; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D009173:Mycophenolic Acid; D002118:Calcium