In vitro resorptive activity of isolated chick osteoclasts: effects of carbonic anhydrase inhibition.
A potent inhibitor of carbonic anhydrase, 5-[3-hydroxybenzoyl]thiophene-2-sulfonamide (HTS), was shown to cause a 37% reduction in the area of resorption pits formed by isolated chick osteoclasts when used at a dose of 10(-7) M. HTS at doses of 10(-9) and 10(-7) M was also effective in reducing acid formation by the osteoclasts (14 and 36%, respectively). Additionally, the effect of HTS was found to be readily reversed by removing the agent, showing that it does not exert a toxic effect on the cells. This study indicates that the inhibitory effect of HTS on bone resorption is at the level of the acid-forming mechanism in osteoclasts and supports the view that carbonic anhydrase has a central role in the process.
Hunter
S J
SJ
Department of Zoology, University of Maine, Orono 04469.
Rosen
C J
CJ
Gay
C V
CV
D000135:Acid Phosphatase; D000165:Acridine Orange; D000818:Animals; D001862:Bone Resorption / Q000201:enzymology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D002645:Chickens; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology; D013644:Tartrates; D013876:Thiophenes / Q000494:pharmacology* / Q000633:toxicity
D002257:Carbonic Anhydrase Inhibitors; D013644:Tartrates; D013876:Thiophenes; C055058:5-(3-hydroxybenzoyl)-2-thiophenesulfonamide; D000135:Acid Phosphatase; D000165:Acridine Orange; C029768:tartaric acid