title: Concanamycin B, a vacuolar H(+)-ATPase specific inhibitor suppresses bone resorption in vitro.
abstract: Effects of concanamycin B, a specific inhibitor of the vacuolar type H(+)-ATPase (V-ATPase), on the stimulation of bone resorption induced by parathyroid hormone (PTH) were examined in vitro. Concanamycin B was found to inhibit PTH-stimulated osteoclastic pit formation and to suppress the acidification of vacuolar organelles by V-ATPase in the osteoclasts. PTH-stimulated 45Ca release from prelabelled chick embryonic calvariae was also inhibited by concanamycin B in a dose-dependent manner. These results suggest that osteoclastic acidification of lacunae by V-ATPase plays an essential role in mineral dissolution and degradation of the organic matrix during bone resorption.
authors.affiliation: Department of Bioengineering, Tokyo Institute of Technology, Kanagawa, Japan.
authors.forename: J T
authors.initials: JT
authors.lastname: Woo
authors.forename: Y
authors.initials: Y
authors.lastname: Ohba
authors.forename: K
authors.initials: K
authors.lastname: Tagami
authors.forename: K
authors.initials: K
authors.lastname: Sumitani
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D018942:Macrolides; D010281:Parathyroid Hormone / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014617:Vacuoles / Q000201:enzymology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D010281:Parathyroid Hormone; C036979:concanamycin B; D006180:Proton-Translocating ATPases; D002118:Calcium