Ouabain Effects on Hormonally-Stimulated Bone Resorption and Cyclic AMP Content in Cultured Fetal Rat Bones

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Abstract
Ouabain in concentrations from 20-100 .mu.M produced a dose-related inhibition of in vitro stimulation of bone resorption by parathyroid hormone, 1,25-dihydroxyvitamin D3 and Ca ionophore A23187 [calcimycin], as measured by 45Ca and [3H]-hydroxyproline release in 5 day cultures of fetal rat forelimb rudiments. The inhibitory effect on 45Ca release was completely reversed by subsequent incubation in ouabain-free medium. At a concentration of 100 .mu.M ouabain virtually abolished active bone resorption; however, basal and stimulated bone cAMP content were significantly increased above levels observed in the absence of ouabain. The increased cAMP content did not appear to be the result of phosphodiesterase inhibition. Intact Na, K ATPase function is required for hormonally-stimulated bone resorptive processes and the inhibitory effect of ouabain on bone resorption is produced at a point subsequent to cAMP generation.