Cloning and characterization of a calcium-sensing receptor from the hypercalcemic New Zealand white rabbit reveals unaltered responsiveness to extracellular calcium

J Bone Miner Res. 1997 Apr;12(4):568-79. doi: 10.1359/jbmr.1997.12.4.568.


The extracellular Ca2+ (Ca(0)2+)-sensing receptor (CaR) recently cloned from mammalian parathyroid, kidney, brain, and thyroid plays a central role in maintaining near constancy of Ca(0)2+. We previously showed that the hypercalcemia normally present in New Zealand white rabbits is associated with an elevated set point for Ca(02+)-regulated PTH release (the level of Ca(0)2+ half-maximally inhibiting hormonal secretion). This observation suggested an alteration in the Ca(02+)-sensing mechanism in the rabbit parathyroid, a possibility we have now pursued by isolating and characterizing the rabbit homolog of the CaR. The cloned rabbit kidney CaR (RabCaR) shares a high degree of overall homology (> 90% amino acid identity) with the bovine, human, and rat CaRs, although it differs slightly in several regions of the extracellular domain potentially involved in binding ligands. By Northern analysis and/or immunohistochemistry, a similar or identical receptor is also expressed in parathyroid, thyroid C cells, small and large intestine, and in the thick ascending limb and collecting ducts of the kidney. When expressed transiently in HEK293 cells and assayed functionally through CaR agonist-evoked increases in Ca(i)2+, the rabbit CaR shows apparent affinities for Ca(0)2+, Mg(0)2+, and Gd(0)3+ that are indistinguishable from those observed in studies carried out concomitantly using the human CaR. Therefore, at least as assessed by its ability to increase Ca(i)2+ when expressed in HEK293 cells, the intrinsic functional properties of the rabbit CaR cannot explain the hypercalcemia observed in vivo in the New Zealand white rabbit.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Blotting, Northern
  • Calcium / metabolism*
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism
  • Cattle
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary / chemistry
  • DNA, Complementary / metabolism
  • Extracellular Space / metabolism*
  • Gadolinium / metabolism
  • Glycosylation
  • Humans
  • Hypercalcemia / genetics*
  • Hypercalcemia / metabolism
  • Kidney / chemistry
  • Magnesium / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Parathyroid Glands / chemistry
  • Protein Structure, Secondary
  • Rabbits
  • Rats
  • Sequence Alignment
  • Tissue Distribution
  • Transfection


  • Calcium-Binding Proteins
  • DNA, Complementary
  • Gadolinium
  • Magnesium
  • Calcium

Associated data