Premium
Human PTH‐(3–34) inhibited the effects of human parathyroid hormone‐related protein on phosphate uptake in a cultured renal cell line (OK cells)
Author(s) -
Nakai Masamichi,
Fukase Masaaki,
Yamaguchi Toru,
Tsukamoto Tatsuo,
Fujii Nobutaka,
Fujita Takuo
Publication year - 1990
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650051002
Subject(s) - endocrinology , medicine , parathyroid hormone , forskolin , chemistry , phosphate , stimulation , receptor , biology , calcium , biochemistry
The action mechanism of hPTH and hPTHrP‐(1–34) on phosphate uptake in opossum kidney (OK) cells was studied using [Nle 8,18 Tyr 34 ]hPTH‐(3–34)‐NH 2 , a potent competitive inhibitor of adenylate cyclase‐coupled PTH receptor. We examined the effects of hPTH‐(1–34), hPTHrP‐(1–34), and hPTH‐(3–34) separately or in combination on the change in renal cyclic AMP production and phosphate uptake in OK cells. Both hPTH‐(1–34) and hPTHrP‐(1–34) stimulated intracellular cyclic AMP production to the same degree at concentrations between 10 −10 and 10 −7 M and inhibited phosphate uptake equipotently on a molar basis (27.5 ± 2.0 and 33.2 ± 1.2% inhibition at 10 −7 M, respectively). Both exogenous addition of (Bu) 2 cAMP and endogenous stimulation of cAMP by forskolin inhibited phosphate uptake in a dose‐dependent manner. Cyclic AMP production induced by either hPTH‐(1–34) or hPTHrP‐(1–34) was inhibited by both [Nle 8,18 Tyr 34 ]‐hPTH‐(3–34)‐NH 2 and [Tyr 34 ]‐hPTH‐(7–34)‐NH 2 . However, [Nle 8,18 Tyr 34 ]hPTH‐(3–34)‐NH 2 and [Tyr 34 ]‐hPTH‐(7–34)‐NH 2 inhibited hPTH‐induced cAMP production more strongly. The inhibitory action of phosphate uptake by hPTH‐(1–34) and hPTHrP‐(1–34) was prevented in the presence of a 100‐fold greater concentration of [Nle 8,18 Tyr 34 ]hPTH‐(3–34)‐NH 2 . The antagonistic action of [Nle 8,18 Tyr 34 ]hPTH‐(3–34)‐NH 2 on the inhibition of phosphate uptake induced by hPTH‐(1–34) and hPTHrP‐(1–34) became weaker with time (0–120 minutes), and [Nle 8,18 Tyr 34 ]hPTH‐(3–34)‐NH 2 did not antagonize the inhibition of phosphate uptake induced by hPTHrP‐(1–34) at 120 minutes of incubation. Our results indicated that PTHrP inhibits renal phosphate transport, at least in part through an adenylate cyclase‐cAMP‐coupled PTH receptor, but the response to the competitive inhibition of this peptide‐induced cAMP production and inhibition of phosphate uptake with PTH receptor antagonists was different. PTH receptor heterogeneity in OK cells may exist and contribute to this phenomenon.