The N-terminal portion of parathyroid hormone-related protein mediates the inhibition of apical Na+/H+ exchange in opossum kidney cells

Shigeto Maeda, Shouxing Wu, Jacob Green, Hyunsook Kim, Ricardo Bosch, Ivan Lee, John Adams, Thomas Clemens, Ira Kurtz

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Abstract

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) can activate a common receptor in several different cell types. Both PTH and N-terminal 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 investigated. In addition, the signal transduction events associated with PTHrP inhibition of apical Na+/H+ exchange in polarized OK-P cells were characterized. Both PTHrP-(134)NH2 and recombinant full-length PTHrP-(1-141) inhibited apical Na+/H+ exchange activity by approximately 50%. These changes occurred in close temporal association with significant (threefold) increases in cellular cAMP accumulation. PTHrP-(1-34)NH2 had no effect on intracellular Ca2+, inositol phosphate production, or protein kinase C activity. PTHrP peptides, including PTHrP-(38-64)NH2, PTHrP-(6786)NH2, PTHrP-(102-107)NH2, and PTHrP-(107-139)NH2, which lack the PTH-like N terminus, had no effect on the antiporter activity or cAMP accumulation. The results demonstrate that the N- terminal portion of the PTHrP molecule is responsible for inhibition of the apical Na+/H+ antiporter in OK-P cells.

Original languageEnglish (US)
Pages (from-to)175-181
Number of pages7
JournalJournal of the American Society of Nephrology
Volume9
Issue number2
Publication statusPublished - Feb 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

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