Stimulation of bone resorption in organ culture by cholera toxin.
Stimulation of bone resorption in organ culture by cholera toxin.
复制标题
霍乱毒素刺激器官培养中的骨吸收。
DOI：
10.1016/0006-291x(81)91645-4
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发表时间：
1981
影响因子：
3.1
通讯作者：
Ivey,JL
中科院分区：
文献类型：
--
作者：
TashjianJr,AH;Ivey,JL
新生小鼠颅骨器官培养物中的骨吸收以剂量相关的方式（0.5至5.0 ng/ml）被choleragen（霍乱肠毒素）刺激。环核苷酸磷酸二酯酶抑制剂异丁基甲基黄嘌呤（4 μM）可增强刺激作用，人降钙素（100 ng/ml）可抑制刺激作用，但吲哚美辛（0.7 μM）（一种脂肪酸环氧合酶抑制剂）不抑制刺激作用。胆碱原对环磷酸腺苷积累和骨吸收的作用与这种毒素的已知特征一致：1。胆固醇增加骨培养物中环磷酸腺苷的积累; 2.在加入胆固醇原后，在环AMP积累增加之前有一个滞后期（20 - 120分钟）; 3.与choleragen孵育仅4小时刺激骨吸收在随后的44小时一样多，连续孵育48小时;和4.生物学上无活性的类霍乱毒素在霍乱原有活性的浓度范围内不刺激骨吸收。我们的结论是腺苷酸环化酶的激活和随后的增加，在环磷酸腺苷生产可以刺激骨吸收，和环磷酸腺苷，因此，可能参与增强骨吸收介导的甲状旁腺激素和其他药物，增加环磷酸腺苷在骨。
Bone resorption in organ cultures of neonatal mouse calvaria was stimulated by choleragen (cholera enterotoxin) in a dose-related manner (0.5 to 5.0 ng/ml). Stimulation was potentiated by the cyclic nucleotide phosphodiesterase inhibitor isobutylmethylxanthine (4 μM) and was inhibited by human calcitonin (100 ng/ml), but not by indomethacin (0.7 μM), an inhibitor of the fatty acid cyclooxygenase. The action of choleragen on cyclic AMP accumulation and bone resorption was consistent with the known characteristics of this toxin: 1. choleragen increased cyclic AMP accumulation in bone cultures; 2. there was a lag period (20 – 120 min) prior to an increase in cyclic AMP accumulation following addition of choleragen; 3. incubation with choleragen for only 4 h stimulated bone resorption in the subsequent 44 h as much as did continuous incubation with choleragen for 48 h; and 4. choleragenoid, the biologically inactive toxoid, did not stimulate bone resorption in the concentration range in which choleragen was active. We conclude that activation of adenylyl cyclase and the subsequent increase in cyclic AMP production can stimulate bone resorption, and that cyclic AMP may, therefore, be involved in the enhanced bone resorption mediated by parathyroid hormone and other agents which increase cyclic AMP in bone.