Na+/H+ antiporter is the primary proton transport system used by osteoclasts during bone resorption.
We have examined the effects of inhibitors of proton transport systems on osteoclastic bone resorption using an in vitro bone slice assay, where osteoclasts (OCs) are free from the influence of other bone cells. Amiloride (AM) and dimethylamiloride (DMA), inhibitors of the Na+/H+ antiporter, were potent inhibitors of bone resorption (IC50 approximately 9 and 0.7 microM for AM and DMA, respectively). Omeprazole (OM), a potent inhibitor of parietal cell K+/H+(-)ATPase, was a poor inhibitor of OC bone resorption (IC50 approximately 100 microM). These results strongly suggest that the Na+/H+ antiporter is the primary proton system used by OCs during bone resorption.
Hall
T J
TJ
Merrell Dow Research Institute, Strasbourg, France.
Chambers
T J
TJ
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D001862:Bone Resorption / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole