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Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid

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Abstract

MAINTENANCE of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca2+-sensing mechanism that also rec-ognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion1–4. The latter restores normocalcaemia by acting on kidney and bone2. We now report the cloning of complementary DNA encoding an extracellular Ca2+ -sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel ∼120K receptor shares limited similarity with the metabotropic glutamate receptors5 and features a large extracellular domain, containing clusters of acidic aminoacid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.

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Author notes

  1. Gerardo Gamba

    Present address: Department of Nephrology, Institute Nacional de la Nutricion Salvador Zubiran, Tlalpan, 14000, Mexico City, Mexico

  2. Adam Sun

    Present address: Renal Division, Department of Medicine, Brown University, Rhode Island, 02963, USA

Authors and Affiliations

  1. Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Edward M. Brown, Robert Butters & Olga Kifor

  2. Harvard Center for the Study of Kidney Disease, Harvard Medical School and Laboratory of Molecular Physiology and Biophysics, Renal Division, Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts, 02115, USA

    Gerardo Gamba, Daniela Riccardi, Michael Lombardi, Adam Sun, Matthias A. Hediger, Jonathan Lytton & Steven C. Hebert

Authors
  1. Edward M. Brown
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  2. Gerardo Gamba
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  3. Daniela Riccardi
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  4. Michael Lombardi
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  5. Robert Butters
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  6. Olga Kifor
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  8. Matthias A. Hediger
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  9. Jonathan Lytton
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  10. Steven C. Hebert
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Brown, E., Gamba, G., Riccardi, D. et al. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 366, 575–580 (1993). https://doi.org/10.1038/366575a0

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  • DOI: https://doi.org/10.1038/366575a0

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