Concanamycin B, a vacuolar H(+)-ATPase specific inhibitor suppresses bone resorption in vitro.
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.
Woo
J T
JT
Department of Bioengineering, Tokyo Institute of Technology, Kanagawa, Japan.
Ohba
Y
Y
Tagami
K
K
Sumitani
K
K
Yamaguchi
K
K
Tsuji
T
T
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*
D000900:Anti-Bacterial Agents; D018942:Macrolides; D010281:Parathyroid Hormone; C036979:concanamycin B; D006180:Proton-Translocating ATPases; D002118:Calcium