Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A.

Abstract

The ionophores A23187 and X-537A were used as probes to investigate the possible role of calcium uptake by bone as a mediator for the stimulation of bone resorption induced by parathyroid hormone (PTH) and other agents in cultured mouse calvaria. The ionophores alone at concentrations from 1 nM to 20 muM did not stimulate bone resorption, nor did they potentiate bone resorption stimulated by submaximal concentrations of PTH after either brief (15-60 min) or extended (1-3 day) exposure to the ionophores. Unexpectedly, we found that the ionophores inhibit in a dose-dependent manner bone resorption stimulated by PTH and a wide variety of other compounds (prostaglandin E2, 1alpha-hydroxycholecalciferol, 3-isobutyl-1-methyl-xanthine, and phorbol myristate acetate). This inhibition was not due to irreversible damage to the bones by the ionophores, because the inhibition was reversible even after 24 h of treatment. Inhibition of bone resorption by the ionophores was observed in media of both high and low calcium concentration, indicating that the inhibition was not due to a critical extracellular calcium concentration. Inhibition by the ionophores differs qualitatively in several ways from that produced by calcitonin, a natural inhibitor of bone resorption. Furthermore, A23187 at 1.0 mug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH- or calcitonin treated calvaria. We conclude that the ionophores A23187 or X537A do not stimulate bone resorption nor potentiate the effects of stimulators of bone resorption; instead they are inhibitors of bone resorption stimulated by a wide variety of compounds.

• Authors: J L Ivey, D R Wright, A H Tashjian Jr
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 58 Issue 6 Pg. 1327-38 (Dec 1976) ISSN: 0021-9738 [Print] United States
• PMID: 186489 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Parathyroid Hormone
• Calcimycin
• Calcitonin
• Cyclic AMP
• Calcium
• Lasalocid

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Bone Resorption (drug effects)
• Bone and Bones (analysis)
• Calcimycin (pharmacology)
• Calcitonin (physiology)
• Calcium (physiology)
• Cyclic AMP (analysis)
• Lasalocid (pharmacology)
• Mice
• Organ Culture Techniques
• Parathyroid Hormone (pharmacology)
• Time Factors