Parathyroid hormone stimulates bone resorption via a Na-Ca exchange mechanism

Parathyroid hormone (PTH) stimulates the release of calcium from bone and is thought to initiate its action by a direct effect on the plasma membrane of bone cells. Although specific membrane receptors for PTH have not yet been identified in bone, they have been characterized in kidney, and PTH does stimulate production of cyclic AMP in bone. However, the mechanism by which PTH causes the release of Ca from bone is not understood. We have determined that several agents that alter ion transport across biological membranes inhibit PTH-stimulated bone resorption in vitro. These agents include ouabain, veratridine and certain monovalent cation ionophores, which transport monovalent cations selectively. The inhibition of bone resorption is dose dependent and reversible within the first 24 h of treatment. All these compounds would be expected to increase intracellular sodium concentration in bone cells. Also, we find that decreasing the extracellular Na+ concentration prevents PTH-stimulated resorption. Therefore, we propose that PTH acts on bone to stimulate Ca release by means of a Na-Ca exchange mechanism. Decreasing the Na gradient across the bone cell plasma membrane would prevent the Na-Ca exchange and thus inhibit the physiological response to PTH.