INHIBITION OF BONE-RESORPTION BY H+ K+-ATPASE INHIBITORS/

We have found that onyl)-8-methoxy-4-((2-methylphenyl)amino)quinoline (1, CP-113,411), a reversible inhibitor of gastric H+/K+-ATPase (IC50 10-20 mM), is also a potent inhibitor of bone resorption by osteoclast s in a bone slice assay at concentrations as low as 10(-7) M, with an IC50 of 2 mM. By contrast, the structurally related H+/K+-ATPase inhib itor 2 nyl)-8-methoxy-4-((2-methylphenyl)amino)quinoline) disclosed by Robins is slightly more potent as an inhibitor of the gastric enzyme (IC50 3-10 muM in our hands) but less efficacious than 1 as an inhibit or of osteoclasts in the bone slice assay at the lower concentrations (no effect at less-than-or-equal-to 10(-6) M, IC50 4 mM). These findin gs suggest that osteoclasts contain an H+/K+-ATPase-like enzyme which differs from the gastric one.