A PHARMACOLOGICAL ASSESSMENT OF THE MAMMALIAN OSTEOCLAST VACUOLAR H-ATPASE()

It is well established that osteoclasts use a vacuolar-type H+-ATPase (V-ATPase) for proton pumping during bone resorption and that specific V-ATPase inhibitors such as bafilomycin Al abolish osteoclastic bone resorption in the bone slice assay. It has been reported that the V-AT Pase in avian osteoclasts can be distinguished from the V-ATPase expre ssed in most other cells, by virtue of its inhibition by vanadate and nitrate ions. In order to determine whether the V-ATPase in mammalian osteoclasts can be similarly distinguished, we have investigated the e ffects of vanadate and nitrate on bone resorption by rat osteoclasts i n the bone slice assay, in comparison with known V-ATPase inhibitors, bafilomycin Al and WY 47766, that also inhibit the chicken osteoclast V-ATPase. The results indicate that, unlike the avian osteoclast V-ATP ase, the mammalian osteoclast V-ATPase is pharmacologically similar to the V-ATPase in other cells.