Inhibition of prostaglandin action and bone resorption by copper.
Mouse calvaria were maintained in organ culture without serum additives. The effects of Cu2+ on bone resorption and on the synthesis and action of prostaglandins were studied. Non-toxic concentrations of copper sulphate (5 microM) were found to decrease active resorption, measured by 45Ca release, to 54% control values (p less than 0.001), while prostaglandin F (PGF), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha, (6-keto-PGF1 alpha), determined by radioimmunoassay, were increased above controls (p less than 0.05). These effects of Cu2+ on prostaglandin synthesis were confirmed by the isolation and quantitation of [3H]-labelled metabolites released from calvaria which had been pre-labelled with [3H]-arachidonic acid. PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) were all higher in copper-exposed calvaria, but their relative amounts remained unchanged. There was no evidence that Cu2+ influenced the mobilisation of [3H]-arachidonic acid from prelabelled calvaria. The stimulation of bone resorption by exogenous prostaglandins was decreased in the presence of Cu2+ (p less than 0.005), while parathormone-mediated bone resorption was virtually unaffected. Cu2+ also increased the inhibition of bone resorption seen with indomethacin (p less than 0.05). In addition to the effects of the metal on prostaglandin action Cu2+ also decreased beta-glucuronidase activity in the media to 86% of the control values (p less than 0.001). The action of Cu2+ in inhibiting bone resorption in vitro appears complex but does not involve inhibition of prostaglandin synthesis. It is likely that Cu2+ has more than one inhibitory locus.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003300:Copper; D015232:Dinoprostone; D007213:Indomethacin