THE N-TERMINAL PORTION OF PARATHYROID HORMONE-RELATED PROTEIN MEDIATES THE INHIBITION OF APICAL NA+ H+ EXCHANGE IN OPOSSUM KIDNEY-CELLS/

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) can activate a common receptor in several different cell types. Both PTH and N-ter minal PTHrP peptides have been shown to acutely inhibit the apical Na/H+ exchanger in the renal proximal tubule. In this study, the ability of various PTHrP fragments to inhibit apical Na+/H+ exchange was inve stigated. In addition, the signal transduction events associated with PTHrP inhibition of apical Na+/H+ exchange in polarized OK-P cells wer e characterized. Both PTHrP-(1-34)NH2 and recombinant full-length PTHr P-(1-141) inhibited apical Na+/H+ exchange activity by approximately 5 0%. These changes occurred in close temporal association with signific ant (threefold) increases in cellular cAMP accumulation. PTHrP-(1-34)N H2 had no effect on intracellular Ca2+ inositol phosphate production, or protein kinase C activity. PTHrP peptides, including PTHrP-(38-64)N H2, PTHrP-(67-86)NH2, PTHrP-(102-107)NH2, and PTHrP-(107-139)NH2, whic h lack the PTH-like N terminus, had no effect on the antiporter activi ty or cAMP accumulation. The results demonstrate that the N-terminal p ortion of the PTHrP molecule is responsible for inhibition of the apic al Na+/H+ antiporter in OK-P cells.