Inhibition of stimulated bone resorption by vanadate.
We have previously reported that stimulated release of calcium (Ca) from bone is a sodium-dependent process. Partial support for this conclusion came from the observation that ouabain inhibited stimulated bone resorption as a result of inhibition of the Na,K-ATPase in bone. We now present additional supporting evidence from the results of experiments using vanadate, an ion known to inhibit the activity of Na,K-ATPase. Vanadate inhibited stimulated bone resorption in neonatal mouse calvaria. Inhibition occurred in a dose-dependent manner, and ortho-vanadate was 3-fold more potent than meta-vanadate. Ortho-vanadate was equally effective against several different stimulators of resorption, including PTH, prostaglandin E2, and 1,25-dihydroxycholecalciferol. PTH-stimulated bone resorption was inhibited with a Ki of about 9 microM. Stimulated Ca release was completely blocked whether vanadate was added at zero time or 24 h after the addition of a resorption-stimulating agent. Because the responses to vanadate were similar to those observed with ouabain, we conclude that vanadate is probably acting to inhibit stimulated resorption via inhibition of the Na,K-ATPase in bone.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014639:Vanadium / Q000494:pharmacology*
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D014639:Vanadium; D010042:Ouabain; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D002118:Calcium