Parathyroid hormone exerts an important control over reabsorption of calcium by the renal tubules which is a major component in the regulation of calcium in extracellular fluids. Previous studies have demonstrated that activation of adenylate cyclase and production of adenosine 3, 5-phosphate (cAMP) is an initial step in the action of PTH on renal target cells. Changes in cAMP concentrations are thought to mediate certain intracellular responses involved in transport of calcium through tubule cells, although the specific mode of this cAMP mediation is unknown. The proposed investigation is designed to provide additional information regarding relationships between cAMP-dependent protein kinase activity and calcium transport in subcellular fractions from isolated renal cortical tubules enriched for proximal or distal segments. The specific objectives are the following: 1. To determine if relationships exist within intact renal cortical cells between endogenous cAMP, protein kinase activity and transport of calcium in response to PTH. 2. To determine the distribution of endogenous substrate proteins phosphorylated following incubation of renal tubule cells in PTH. 3. To determine if relationships exist between cyclic AMP-dependent phosphorylation and changes in calcium transport properties within plasma membranes and microsomes from renal cortical cells. Data obtained from these studies should provide additional important information concerning mechanisms by which PTH influences calcium transport in renal tubules. An understanding of this process has important implication in the successful management of a variety of renal-related calcium imbalances known to occur in man.
