Cooper C W, Yi S J, Seitz P K
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
J Bone Miner Res. 1988 Apr;3(2):219-23. doi: 10.1002/jbmr.5650030215.
Baby rat thyroid glands and cultured rat medullary carcinoma C cells were incubated acutely with phenytoin (38-100 microM), and the calcitonin (CT) secreted into the serum-free medium was measured by radioimmunoassay (RIA). Phenytoin did not alter CT release from glands or C cells incubated in 1 mM Ca, but, when Ca was raised to 1.75 or 2.5 mM, a marked inhibitory effect of phenytoin was apparent. The inhibitory effect could be negated by including 10 microM BAY-K-8644 in the medium. Inhibitory effects on CT release also were obtained with 100 microM trifluoperazine or 100 microM nitrendipine, and these inhibitory effects also were counteracted by 10 microM BAY-K-8644. The results show that clinically relevant amounts of phenytoin can inhibit CT release, perhaps by interfering with C-cell Ca channels or by inhibiting calmodulin-dependent processes.
将新生大鼠甲状腺及培养的大鼠髓样癌C细胞与苯妥英（38 - 100微摩尔）进行急性孵育，采用放射免疫分析法（RIA）测定分泌到无血清培养基中的降钙素（CT）。在1毫摩尔钙浓度下孵育时，苯妥英不会改变腺体或C细胞释放CT的情况，但是，当钙浓度升高到1.75或2.5毫摩尔时，苯妥英的显著抑制作用就很明显了。在培养基中加入10微摩尔BAY - K - 8644可消除这种抑制作用。100微摩尔三氟拉嗪或100微摩尔尼群地平也对CT释放有抑制作用，并且这些抑制作用同样可被10微摩尔BAY - K - 8644抵消。结果表明，临床相关剂量的苯妥英可能通过干扰C细胞钙通道或抑制钙调蛋白依赖性过程来抑制CT释放。
