EXPRESSION CLONING OF A COMMON RECEPTOR FOR PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE FROM RAT OSTEOBLAST-LIKE CELLS - A SINGLE RECEPTOR STIMULATES INTRACELLULAR ACCUMULATION OF BOTH CAMP ANDINOSITOL TRISPHOSPHATES AND INCREASES INTRACELLULAR FREE CALCIUM

Parathyroid hormone (PTH), a major regulator of mineral ion metabolism , and PTH-related peptide (PTHrP), which causes hypercalcemia in some cancer patients, stimulate multiple signals (cAMP, inositol phosphates , and calcium) probably by activating common receptors in bone and kid ney. Using expression cloning, we have isolated a cDNA clone encoding rat bone PTH/PTHrP receptor from rat osteosarcoma (ROS 17/2.8) cells. The rat bone PTH/PTHrP receptor is 78% identical to the opossum kidney receptor; this identity indicates striking conservation of this recep tor across distant mammalian species. Additionally, the rat bone PTH/P THrP receptor has significant homology to the secretin and calcitonin receptors but not to any other G protein-linked receptor. When express ed in COS cells, a single cDNA clone, expressing either rat bone or op ossum kidney PTH/PTHrP receptor, mediates PTH and PTHrP stimulation of both adenylate cyclase and phospholipase C. These properties could ex plain the diversity of PTH action without the need to postulate other receptor subtypes.