Oxatomide and calcium: mechanisms involved in the secretion of mast cell mediators

Human cutaneous mast cells and their experimental model rat peritoneal mast cells, can be stimulated by an IgE-dependent process or by peptides through the direct activation of G proteins. Both activation pathways lead to the increase of cytosolic Ca2+ level. This increase in dependent of the mobilisation of intracellular calcium stores of the endoplasmic reticulum involving the stimulation of IP3-sensitive calcium channels. Mast cells are characterized by the absence of calcium channels in the plasma membrane. Oxatomide has been synthetized as an analog of cinnarizine. However oxatomide is inactive on current calcium channels. In mast cells, oxatomide inhibits the increase of cytosolic calcium elicited during mast cell activation. Consequently mast cell exocytosis is inhibited altogether with the release of newly synthetized mediators. The authors propose several putative targets for oxatomide in mast cells. The therapeutic effect of oxatomide is also related to its property to antagonize the effects of anaphylactic mediators on their selective receptors.