Cellular calcium has a pivotal regulatory role in many aspects of: 1) normal physiology, such as hormone secretion, control of other intracellular messengers and modulation of cancer-promoting oncogenes; and 2) human disease (calcium is a pathogenic factor in the neuronal damage due to stroke, epilepsy and hypoglycemia). With hormone secretion from rat anterior pituitary cells as the model system, the broad objective of this program is to learn how normal cells control calcium ion movements and calcium concentration and compare this knowledge with observations in cancer cells where calcium-dependent activities are abnormal. Endogenous hypothalamic hormones or selected pharmacologic agents will be applied to cultured normal or neoplastic anterior pituitary cells to perturb the intrinsic systems modulating calcium flux as the cell executes its biological role of hormone secretion. The intracellular calcium concentrations will be measured with an intracellular fluorescent probe, Indo-1, during perifusion of the pituitary cells to allow concomitant analysis of the hormone secretory rate. These investigations will shed light on the normal mechanisms governing calcium ion flux and the alterations that confer neoplastic properties upon certain cells. The experimental procedures required to complete this project are established and the preliminary work demonstrates feasibility.
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