Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture

N. S. Krieger, T. S. Stappenbeck, P. H. Stern

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse of calvaria and fetal rat limb bones. Threshold doses were 0.1 μM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations below 0.1 mM did not effect calvarial cyclic AMP. 0.5 μM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones. 3 nM calcitonin inhibited milrinone-stimulated resorption and there was no escape from this inhibition. Structural homology between milrinone and thyroxine has been reported. We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition.

Original languageEnglish (US)
Pages (from-to)444-448
Number of pages5
JournalJournal of Clinical Investigation
Volume79
Issue number2
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Medicine(all)

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