Sensitivity to nitrate and other oxyanions further distinguishes the vanadate-sensitive osteoclast proton pump from other vacuolar hydrogen ion-ATPases
- 23 March 1993
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 32 (11), 2808-2812
- https://doi.org/10.1021/bi00062a011
Abstract
The osteoclast proton pump (OC H(+)-ATPase) differs from other vacuolar H(+)-ATPases (V-ATPases) in its sensitivity to vanadate and in the subunit composition of its catalytic domain, where isoforms of subunits A and B are expressed [Chatterjee et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6257-6261]. In the present study, the sensitivity of the osteoclast H(+)-ATPase to various oxyanions was tested. The results indicate that H+ transport by microsomal preparations isolated from chicken osteoclasts is 20-100-fold more sensitive to nitrate that any other animal and fungal V-ATPases and 10-20-fold more sensitive than plant V-ATPases, as is the ATPase activity of the affinity-purified enzyme. This inhibition by nitrate is not due to a chaotropic effect of the oxyanion and is complete at 1 mM concentrations with an IC50 of 100 microM. In contrast, proton transport by the OC H(+)-ATPase was insensitive to other oxyanions (phosphate, sulfate, and acetate) which inhibit other V-ATPases. These results further demonstrate that the proton pump present in osteoclast membranes differs from other vacuolar ATPases. It is speculated that, since cells of the macrophage lineage can generate high intracellular concentrations of nitrate, it may be possible to physiologically or therapeutically regulate the activity of the OC H(+)-ATPase in the osteoclast without affecting the other V-ATPases in the same or in other cells.Keywords
This publication has 14 references indexed in Scilit:
- Structure and pharmacology of the proton-ATPasesTrends in Pharmacological Sciences, 1991
- Biochemical characterization of an electrogenic vacuolar proton pump in purified chicken osteoclast plasma membrane vesiclesJournal of Bone and Mineral Research, 1990
- Osteoclastic Bone Resorption by a Polarized Vacuolar Proton PumpScience, 1989
- Human endomembrane H+ pump strongly resembles the ATP-synthetase of Archaebacteria.Proceedings of the National Academy of Sciences, 1989
- Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediateBiochemistry, 1988
- Internal anion binding site and membrane potential dominate the regulation of proton pumping by the chromaffin granule ATPaseBiochemical and Biophysical Research Communications, 1987
- Structure of the novel membrane-coating material in proton-secreting epithelial cells and identification as an H+ATPase.The Journal of cell biology, 1987
- Subunit composition and ATP site labeling of the coated vesicle proton-translocating adenosine triphosphataseBiochemistry, 1987
- Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border.The Journal of cell biology, 1985
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970