THE ROLE OF CALCIUM IN SECRETION FROM TUMOR BASOPHILS

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The role of calcium in stimulus-secretion coupling in tumour basophils will be studied. The aim will be to determine the mechanism by which the aggregation of receptors for immunoglobulin E(IgE) leads to an elevation of cytoplasmic Ca++ and the subsequent secretion of histamine, serotonin and other mediators of immediate hypersensitivity. Tracer measurements of 45Ca uptake, efflux and movements at isotopic equilibrium will be used to determine the relative contributions of intracellular calcium stores, plasma membrane extrusion mechanisms and permeability pathways. Since intracellular pH and membrane potential may also affect calcium handling by the cells, these will be measured using radiolabelled ion distribution methods. The intracellular calcium buffer and fluorescence indicator, quin2, will be used to monitor changes in free ionized calcium in the cytoplasm. It will also be used to generate a large cytoplasmic pool of buffered calcium in studies of 45Ca fluxes acrosss the plasma membrane. The long-term objective is the molecular characterization of the calcium permeability pathway or channel and its interactions with receptors for IgE. This should further our understanding of the biochemistry and cell biology of stimulus-secretion coupling and be of value in designing methods and drugs for the treatment of allergies and asthma.