CLONING AND CHARACTERIZATION OF A CALCIUM-SENSING RECEPTOR FROM THE HYPERCALCEMIC NEW-ZEALAND WHITE-RABBIT REVEALS UNALTERED RESPONSIVENESSTO EXTRACELLULAR CALCIUM

The extracellular Ca2+ (Ca-0(2+))-sensing receptor (CaR) recently clon ed from mammalian parathyroid, kidney, brain, and thyroid plays a cent ral role in maintaining near constancy of Ca-0(2+). We previously show ed that the hypercalcemia normally present in New Zealand white rabbit s is associated with an elevated set point for Ca-0(2+)-regulated PTH release (the level of Ca-0(2+) half-maximally inhibiting hormonal secr etion), This observation suggested an alteration in the Ca-0(2+)-sensi ng mechanism in the rabbit parathyroid, a possibility we have now purs ued by isolating and characterizing the rabbit homolog of the CaR, The cloned rabbit kidney CaR (RabCaR) shares a high degree of overall hom ology (>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 a nd/or immunohistochemistry, a similar or identical receptor is also ex pressed in parathyroid, thyroid C cells, small and large intestine, an d in the thick ascending limb and collecting ducts of the kidney, When expressed transiently in HEK293 cells and assayed functionally throug h CaR agonist-evoked increases in Ca-i(2+) the rabbit CaR shows appare nt affinities for Ca-0(2+), Mg-0(2+), and Gd-0(3+) that are indistingu ishable from those observed in studies carried out concomitantly using the human CaR, Therefore, at least as assessed by its ability to incr ease Ca-i(2+) when expressed in HEK293 cells, the intrinsic functional properties of the rabbit CaR cannot explain the hypercalcemia observe d in vivo in the New Zealand white rabbit.