Effect of cholera toxin on histamine release from bone marrow-derived mouse mast cells.
Bone marrow-derived mouse mast cells were sensitized with monoclonal mouse IgE antibody and treated with cholera toxin (CT), which ADP-ribosylated the alpha-subunit of the stimulatory guanine nucleotide-binding regulatory protein Gs, prior to challenge with either antigen or thrombin. The CT treatment increased intracellular cAMP levels, but neither enhanced nor inhibited antigen-induced histamine release or arachidonate release. The same treatment of the sensitized bone marrow-derived mouse mast cells with CT markedly enhanced thrombin-induced histamine release without affecting arachidonate release. The CT treatment failed to affect antigen-induced and thrombin-induced generation of inositol trisphosphate and of diacylglycerol or mobilization of intracellular Ca2+. The results indicate that Gs in bone marrow-derived mouse mast cells is not involved in the transduction of the antigen-induced or thrombin-induced triggering signal to phospholipase C, which initiates the enhancement of phosphatidylinositol turnover. The enhancement of thrombin-induced histamine release by CT treatment with the observations that thrombin-induced histamine release was inhibited by pretreatment of the cells with pertussis toxin suggest that the involvement of a guanine nucleotide-binding regulatory protein in thrombin-induced biochemical events is an event distal to Ca2+ mobilization.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001854:Bone Marrow Cells; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000502:physiology; D066298:In Vitro Techniques; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D010716:Phosphatidylinositols; D000246:Adenosine Diphosphate Ribose; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D002772:Cholera Toxin; D000242:Cyclic AMP; D013917:Thrombin; D019204:GTP-Binding Proteins