Stimulation of uridine incorporation in isolated bone cells by parathyroid hormone and cyclic AMP

William A. Peck, Kirk Messinger, George Kimmich, Janet Carpenter

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    8 Scopus citations

    Abstract

    Treatment of isolated bone cells with purified bovine parathyroid hormone (5 ng/ml-2 μg/ml) augmented the incorporation of 2-14C-uridine into acid-soluble RNA precursor pools and into RNA. Stimulation developed within 15 min and gradually declined after 30 min. A synthetic N-terminal 1-34 amino acid fragment of PTH was one-half as potent as native hormone. A 2-34 amino acid fragment, oxidized native hormone, and several basic polypeptides were inactive. PTH enhanced the labeling of cellular UDP and UTP pools appreciably and increased that of UMP slightly but failed to modify the total radioactivity of cellular free uridine, pointing to uridine or UMP phosphorylation (or both) as the site(s) of PTH action. Stimulation of 2-14C-uridine incorporation was not associated withalterations in total cell ATP levels. The effect of PTH on uridine metabolism appeared during simultaneous treatment of bone cells with actinomycin D, indicating that it was independent of RNAsynthesis. Exogenous (Bt)2 cAMP (0.1-1.0 min) and cAMP (1-2 HIM), but not 5′-AMP or 2′-AMP, increased 2-14C-uridine incorporation. (Bt)2 cAMP exhibited the same time course of action as PTH and mimicked its selective effects on the labeling of cellular free nucleotide pools. Like PTH, (Bt)2 cAMP enhanced the labeling of RNA precursor pools in the presence of actinomycin D and did not increase bone cell ATP. Simultaneous treatment of bone cells with (Bt)2 cAMP and PTH at maximal stimulatoryconcentrations was not significantly more effective than treatment with either agentalone. The stimulatory effects of PTH and (Bt)2 cAMP persisted when previously treated cells were incubated in hormone- and nucleotide-free medium. 2-14C-uridine incorporation was also augmented by theophylline, which is known to raise bone cell cyclic-3′, 5′-AMP levels. These results strongly suggest that cAMP mediates, at least in part, the acute effect of PTH on uridine metabolism.

    Original languageEnglish
    Pages (from-to)289-298
    Number of pages10
    JournalEndocrinology
    Volume95
    Issue number1
    DOIs
    StatePublished - Jul 1974

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