The calcium-sensing receptor is localized in caveolin-rich plasma membrane domains of bovine parathyroid cells

Parathyroid cells have an intracellular machinery for parathyroid hormone (PTH) secretion that is inversely regulated by the extracellular calcium concentration (Ca-0(2+)). The recently characterized Ca-0(2+)-semsing receptor (CaR) is a G protein-coupled, seven-transmembrane receptor mediating the inhibitory effects of high Ca-0(2+) on PTH secretion. The CaR's precise cell surface localization and the signal transducation pathway(s) mediating its inhibitory effects on PTH secretion have not been characterized fully. Here, we demonstrate that the CaR resides within caveolin-rich membrane domains in bovine parathyroid cells. Chief cells within bovine parathyroid glands exhibit a similar pattern of staining for caveolin-1 and for alkaline phosphatase, a glucosylphosphatidylinositol-anchored protein often enriched in caveolae. Purified caveolin-enriched membrane fractions (CEMF) from bovine parathyroid cells are highly enriched in the CaR. and alkaline phosphatase. Other signaling proteins, including G(q/11), eNOS, and several protein kinase C isoforms (i.e. alpha, delta, and zeta, are also present in CEMF, Activation of the CaR by high Ca-0(2+) increases tyrosine phosphorylation of caveolin-1 in CEMF, suggesting that CaR-mediated signal transduction potentially involved in Ca-0(2+)-regulated processes in parathyroid cells occur in caveolae-like domains.