CLONING, EXPRESSION, AND TISSUE LOCALIZATION OF THE CALCIUM-SENSING RECEPTOR IN CHICKEN (GALLUS-DOMESTICUS)

In previous studies, we characterized an extracellular Ca2+ (Ca-o(2+)) -sensing receptor (CaR) that plays a central role in regulating parath yroid hormone secretion in mammals by sensing Ca-o(2+). In the present study, we have cloned and characterized the chicken (Gallus domesticu s) homolog of the CaR. The chicken parathyroid CaR shares a high degre e of homology (84% amino acid identity) with the human CaR and display s a similar topology. Moreover, amino acid residues where mutations ca use disorders of Ca-o(2+)-sensing in the human CaR share the wild-type human sequence in the chicken CaR. However, a single region in the ex tracellular domain of the chicken CaR differs substantially from its m ammalian homologs. Xenopus laevis oocytes injected with chicken CaR cR NA respond to elevated ambient levels of Ca-o(2+), extracellular Mg2+, or extracellular Gd3+ with the characteristic activation of inositol trisphosphate-dependent, intracellular Ca2+-induced Cl- currents elici ted by mammalian CaRs as well as by G protein-linked receptors coupled to activation of phospholipase C. By in situ hybridization, clusters of cells in chicken parathyroid glands were shown to express CaR messe nger RNA. Northern analysis and immunohistochemistry demonstrated expr ession of receptor transcripts and/or protein in kidney tubules and in testine as well as in brain. The close conservation of the amino acid sequence of the chicken CaR with its mammalian homologs as well as its similar tissue distribution suggest that the receptor may also play a n important role in avian calcium homeostasis.