The objectives of this proposal are to study the nephron sites of phosphate reabsorption, the kinetics of phosphate reabsorption, and the regulation of phosphate reabsorption. Specifically, we propose to determine whether phosphate is reabsorbed exclusively in the proximal nephron or also in more distal nephron segments of the rat. In addition we will evaluate the effect of parathyroid hormone on specific nephron segments which demonstrate phosphate transport. Following identification of the sites of phosphate transport, we will develop a new approach for the kinetic description of phosphate reabsorption, as a function of phosphate concentration, for specific segments of individual nephrons. This system, in turn, will provide a tool for evaluation of the effects of factors important in phosphate regulation. Specifically, the effects of microperfusion with calcium free and calcium containing solutions will be evaluated in the presence and absence of ionophores in the microperfusate. Finally, we have found that the golden hamster responds to parathyroid hormone with increases in urinary cyclic AMP but without a phosphaturia. Further, PTH stimulated adenylate cyclase and elevated renal cortical levels of cyclic AMP in the hamster as in animals with a phosphaturic response. This then provides a functional model for pseudohypoparathyroidism type II, which can be evaluated with micropuncture and biochemical techniques in search of a specific defect. These studies have important fundamental implications for understanding the pathophysiology of abnormal phosphate metabolism and its regulation by PTH and the pathogenesis of urolithiasis.