Hall G E, Kenny A D
J Pharmacol Exp Ther. 1986 Sep;238(3):778-82.
The role of carbonic anhydrase in bone resorption induced by parathyroid hormone (PTH) and dibutyryl cyclic AMP (DBcAMP) was studied using an in vitro neonatal mouse half-calvarial culture system. Both PTH (16.7 nM) and DBcAMP (0.3 mM) were effective in stimulating bone resorption, as assessed by measuring changes in media calcium concentrations. Bones treated with PTH or DBcAMP for 96 hr contained significantly greater carbonic anhydrase activity than control bones [PTH Treated/Control (T/C) = 2.44; DBcAMP T/C = 2.34]. Both PTH and DBcAMP significantly enhanced calvarial acid phosphatase activity relative to control values [PTH T/C = 1.48; DBcAMP T/C = 1.30]. Neither PTH nor DBcAMP significantly altered calvarial alkaline phosphatase activity. Bone resorption induced by PTH and DBcAMP was inhibited by the carbonic anhydrase inhibitor acetazolamide, but not by the acetazolamide analog CL 13,850 (N-t-butylacetazolamide), which does not inhibit carbonic anhydrase. These results support the concepts that PTH-induced bone resorption requires the action of osteoclastic carbonic anhydrase and that the action of PTH on bone is mediated, in part, by the action of cyclic AMP.
利用体外新生小鼠半颅骨培养系统，研究了碳酸酐酶在甲状旁腺激素（PTH）和二丁酰环磷腺苷（DBcAMP）诱导的骨吸收中的作用。通过测量培养基钙浓度的变化评估，PTH（16.7 nM）和DBcAMP（0.3 mM）均能有效刺激骨吸收。用PTH或DBcAMP处理96小时的骨骼，其碳酸酐酶活性显著高于对照骨骼[PTH处理组/对照组（T/C）= 2.44；DBcAMP T/C = 2.34]。相对于对照值，PTH和DBcAMP均显著提高了颅骨酸性磷酸酶活性[PTH T/C = 1.48；DBcAMP T/C = 1.30]。PTH和DBcAMP均未显著改变颅骨碱性磷酸酶活性。碳酸酐酶抑制剂乙酰唑胺可抑制PTH和DBcAMP诱导的骨吸收，但不抑制碳酸酐酶的乙酰唑胺类似物CL 13,850（N-叔丁基乙酰唑胺）则无此作用。这些结果支持以下观点：PTH诱导的骨吸收需要破骨细胞碳酸酐酶的作用，且PTH对骨的作用部分是由环磷腺苷介导的。
