Angiotensin II (AII), a potent aldosterone secretagogue, utilizes a number of metabolic and ionic signals to change cellular function in a variety of tissues including: generation of inositol trisphosphate, diacylglycerol, and inositol tetrakisphosphate; Ca2+ influx and mobilization; modification of cell pH; and activation of the Na+/H+ exchanger. However, areas of uncertainty exist as to the participation of these signals in modifying glomerulosa cell (GC) function. First, there is little information concerning the role changes in intracellular hydrogen ion concentration may play in mediating the adrenal response to aldosterone secretagogues, particularly AII. Second, there is little documentation of the presence of a Na+/H+ exchanger in the rat GC, aside from our preliminary results. Third, there is little information on the relationship between Ca2+ and proton changes in GC when stimulated by different aldosterone secretagogues, e.g. the impact of changes in cell hydrogen ion concentration on the response of the phosphoinositide system and/or cytosolic Ca2+ to AII. Fourth, it is not known what mediates the change in adrenal sensitivity to secretagogues with changes in dietary Na+ and K+ intake. Candidates include: a change in the relationship between cytosolic Ca2+ and hydrogen ion and the degree of activation of the phosphoinositide (PI) system. The investigators involved in this study have documented their competency in measuring intracellular concentrations of hydrogen and Ca2+ by fluorescent techniques, the mass and conversion rates of the various components of the PI system, and the rate of activation and types of ion transport processes present in both glomerulosa and vascular smooth muscle tissue. Thus, this team is uniquely qualified to develop an interdisciplinary program to provide answers to these important questions.
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