Responses of fetal rat bone cells and bone organ cultures to the ionophore, A23187

Abstract

The ionophore A23187 produced a rapid transient increase in the rate of calcium uptake by isolated fetal rat bone cells. There was no effect on calcium efflux or total cellular calcium. The magnitude of the effect on influx was amplified when the cell were incubated at 4 degrees C. Cellular metabolic functions and resorption of cultured fetal rat bones (release of 45Ca from pre-labeled long bone) were affected by A23187 in a biphasic manner: cell cyclic AMP (cAMP) was increased by 0.1 and 0.3 mug/ml of the ionophore, whereas 10 mug/ml was either ineffective or lowered the cAMP levels. The high A23187 concentration abolished the stimulatory effects of parathyroid hormone and methylisobutylxanthine. Concentrations of 0.1 and 0.3 mug/ml A23187 stimulated bone resorption. The effect was abolished by calcitonin. Ionophore concentrations above 1 mug/ml produced less bone resorption. These higher concentrations antagonized the bone-resorbing effect of parathyroid hormone and 1,25-dihydroxyvitamin D3. A23187 at 5 and 10 mug/ml decreased bone cell lactate and ATP. Thus at low concentrations, A23187 produced effects on bone similar to those of parathyroid hormone, suggesting that calcium is the primary initiator of PTH-induced bone resorption. At the higher concentrations A23187 may have a general inhibitory effect on cell metabolism.