Lactic acid production in mouse calvaria in vitro with and without parathyroid hormone stimulation: lack of acetazolamide effects.
The effect of acetazolamide on lactic acid production in mouse calvaria explants was examined in an attempt to explain in vivo inhibition of Ca mobilization from bone by sulfonamide inhibitors of carbonic anhydrase. Lactic acid production was evaluated in 8-10-week-old CD-1 mouse calvaria over a time period consistent with acetazolamide inhibition of both PTH-stimulated and nonstimulated Ca mobilization from bone in vivo. Labeled lactate, derived from [3,4-14C]glucose, and total lactate production were determined at 2-h intervals for up to 8 h. Simultaneous assessment of 14CO2 production and [14C]pyruvate levels established that acetazolamide produced no other related metabolic effects and that the drug did not block PTH stimulation of CO2 production. Acetazolamide (4.5 X 10(-4) M) was found to have no effect on labeled or total lactate production in mouse calvaria for up to 8 h of treatment. In addition, acetazolamide did not block PTH (10(-7) M) stimulation of lactate production. However, Cl 13,850 (10(-4) M), a structural analog of acetazolamide devoid of inhibitory activity on carbonic anhydrase or Ca mobilization from bone, was shown to significantly reduce lactate production from mouse calvaria. These results, therefore, suggest that acetazolamide does not inhibit Ca mobilization from bone through inhibition of lactic acid production and fail to support a mechanistic relationship between lactic acid production and Ca mobilization from bone.
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000096:biosynthesis*; D019344:Lactic Acid; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
D007773:Lactates; D010281:Parathyroid Hormone; D013449:Sulfonamides; C037272:Cl 13850; D019344:Lactic Acid; D000086:Acetazolamide; D002118:Calcium