Prostaglandin E2 and 2-chloroadenosine act in concert to stimulate bone resorption in cultured murine calvarial bones.
2-Chloroadenosine-induced calcium release from cultured mouse calvarial bones is reduced by inhibitors of prostaglandin production, whereas PTH stimulated calcium release is not. When calvaria were treated with 2-chloroadenosine (10 microM) for 48 hr the production of PGE was significantly increased. The stimulation of PGE synthesis was totally inhibited by indomethacin (1 microM) and partially by hydrocortisone (0.1 microM). When PGE2 and 2-chloroadenosine, at submaximal concentrations, were simultaneously added to cultures of calvarial bones, in which the endogenous production of prostaglandins was reduced by indomethacin, a supraaditive effect on calcium mobilization by the two agents was seen. No such synergism could be observed between PGE2 and PTH or between 2-chloroadenosine and PTH. The degree of stimulation in indomethacin-treated bones by 2-chloroadenosine (i.e. when compared to indomethacin-treated controls) was almost the same as that seen in bones stimulated by 2-chloroadenosine in the absence of indomethacin. These data suggest that 2-chloroadenosine can induce bone resorption by a mechanism independent of stimulation of prostaglandin synthesis but that the amount of 2-chloroadenosine stimulated resorption is enhanced by endogenous and exogenous PGE2.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D012886:Skull / Q000378:metabolism
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D015762:2-Chloroadenosine; D000241:Adenosine; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin