Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretionCitation formats

  • External authors:
  • Patricia Centeno
  • Amanda Herberger
  • Hee-Chang Mun
  • Chialing Tu
  • Edward F. Nemeth
  • Wenhan Chang
  • Arthur D. Conigrave

Standard

Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. / Centeno, Patricia; Herberger, Amanda; Mun, Hee-Chang; Tu, Chialing; Nemeth, Edward F.; Chang, Wenhan; Conigrave, Arthur D.; Ward, Donald.

In: Nature Communications, Vol. 10, 4693, 16.10.2019.

Research output: Contribution to journalArticlepeer-review

Harvard

Centeno, P, Herberger, A, Mun, H-C, Tu, C, Nemeth, EF, Chang, W, Conigrave, AD & Ward, D 2019, 'Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion', Nature Communications, vol. 10, 4693. https://doi.org/10.1038/s41467-019-12399-9

APA

Centeno, P., Herberger, A., Mun, H-C., Tu, C., Nemeth, E. F., Chang, W., Conigrave, A. D., & Ward, D. (2019). Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. Nature Communications, 10, [4693]. https://doi.org/10.1038/s41467-019-12399-9

Vancouver

Centeno P, Herberger A, Mun H-C, Tu C, Nemeth EF, Chang W et al. Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. Nature Communications. 2019 Oct 16;10. 4693. https://doi.org/10.1038/s41467-019-12399-9

Author

Centeno, Patricia ; Herberger, Amanda ; Mun, Hee-Chang ; Tu, Chialing ; Nemeth, Edward F. ; Chang, Wenhan ; Conigrave, Arthur D. ; Ward, Donald. / Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. In: Nature Communications. 2019 ; Vol. 10.

Bibtex

@article{40f08264698b474ca0aee87065658c2c,
title = "Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion",
abstract = "Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). How- ever, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.",
author = "Patricia Centeno and Amanda Herberger and Hee-Chang Mun and Chialing Tu and Nemeth, {Edward F.} and Wenhan Chang and Conigrave, {Arthur D.} and Donald Ward",
year = "2019",
month = oct,
day = "16",
doi = "10.1038/s41467-019-12399-9",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion

AU - Centeno, Patricia

AU - Herberger, Amanda

AU - Mun, Hee-Chang

AU - Tu, Chialing

AU - Nemeth, Edward F.

AU - Chang, Wenhan

AU - Conigrave, Arthur D.

AU - Ward, Donald

PY - 2019/10/16

Y1 - 2019/10/16

N2 - Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). How- ever, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.

AB - Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). How- ever, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.

U2 - 10.1038/s41467-019-12399-9

DO - 10.1038/s41467-019-12399-9

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4693

ER -