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-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-(1-34)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-(67-86)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.
Maeda
S
S
Division of Endocrinology, Cedars Sinai Medical Center, Cincinnati, Ohio, USA.
Wu
S
S
Green
J
J
Kim
H
H
Bosch
R
R
Lee
I
I
Adams
J
J
Clemens
T L
TL
Kurtz
I
I
D000818:Animals; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D016764:Cell Polarity; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D007295:Inositol Phosphates / Q000032:analysis; D007684:Kidney Tubules / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011493:Protein Kinase C / Q000032:analysis; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013997:Time Factors
D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; D017923:Sodium-Hydrogen Exchangers; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium; D016257:Fura-2