RECEPTOR MECHANISMS IN HEPATOCYTES

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The general goal of this project is to understand better the mechanisms by which hormone receptors regulate ion fluxes in the liver. Emphasis will be placed on cellular mechanisms making use of ion transport measurements and intracellular Ca++ indicators. The significance of this research is twofold: First, understanding these receptor mechanisms in the liver is relevant to the pathophysiology of diabetes since these same receptors regulate the release of glucose into the blood from the liver. Second, similar receptor-ion interactions are involved in a wide variety of health related functions, including vascular reactivity and CNS functions. The initial studies in this project will focus on a quantitative evaluation of hormone induced efflux of K+ which is believed to be mediated by an elevation of intracellular ionized Ca++. Changes in K+ flux will be determined by use of 86Rb flux and a cellular perifusion system. Changes in cytosolic Ca++ will be detecterd by quin-2 fluorescence. The number and regulation of K+ channels will be probed by 125I-apamin binding. An hypothesis as to a specific mechanism for hormone induced intracellular Ca release will be investigated. Specifically, the role of soluble inositol phosphates, as second messengers or cellular Ca modulators will be examined.