HUMAN SYNTHETIC CALCITONIN GENE-RELATED PEPTIDE INHIBITS BONE-RESORPTION INVITRO
HUMAN SYNTHETIC CALCITONIN GENE-RELATED PEPTIDE INHIBITS BONE-RESORPTION INVITRO
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DOI：
10.1210/endo-119-1-58
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发表时间：
1986-07-01
期刊：
影响因子：
4.8
通讯作者：
MUNDY, GR
中科院分区：
文献类型：
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作者：
DSOUZA, SM;MACINTYRE, I;MUNDY, GR
降钙素基因相关肽（CGRP）是一种正常循环的肽。它由降钙素基因编码，其确切功能尚不清楚。由于最近已经显示人CGRP（hCGRP 0）降低大鼠和兔的血浆钙水平，我们检查了人合成CGRP对由PTH、前列腺素E2和1，25-二羟维生素D3刺激的骨吸收（通过45 Ca释放测量）的体外作用。CGRP对PTH刺激的再吸收产生剂量依赖性抑制，在约5 × 10 - 6时抑制率为50%。10-8 M CGRP。CGRP对PTH介导的骨吸收的抑制作用不是由于毒性作用，因为骨与CGRP预孵育48小时，随后能够响应PTH。CGRP在大鼠中的抑制活性比人降钙素的抑制活性低约3个数量级。与降钙素的作用相反，在持续存在CGRP的情况下，96小时后仍观察到对PTH刺激的骨吸收的显著抑制，CGRP 10 ~（-6）~ 10 ~（-8）M也以剂量依赖的方式抑制前列腺素和1，25-二羟维生素D_3刺激的骨吸收，但对基础骨吸收无显著影响。总之，这些数据表明，hCGRP抑制骨吸收刺激在体外。尽管CGRP在大鼠中的效力低于降钙素，但已显示CGRP在其他物种中具有与降钙素相当的效力，因此，不能排除CGRP作为治疗剂在骨吸收增加状态中的作用。
The calcitonin gene-related peptide (CGRP) is a peptide which normally circulates. It is encoded by the calcitonin gene, whose precise function is unknown. Since it has recently been shown that human CGRP (hCGRP0 lowers plasma calcium levels in both the rat and the rabbit, we examined the in vitro effects of human synthetic CGRP on bone resorption (as measured by 45Ca release) stimulated by PTH, prostaglandin E2, and 1,25-dihydroxyvitamin D3. CGRP caused a dose-dependent inhibition of PTH-stimulated resorption, with 50% inhibition at approximately 5 .times. 10-8 M CGRP. The inhibitory effects of CGRP on PTH-mediated bone resorption were not due to toxic effects, since bones preincubated with CGRP for 48 h were subsequently able to respond to PTH. The inhibitory activity of CGRP in the rat was approximately 3 orders of magnitude less potent than that of human calcitonin. In contrast to the effects of calcitonin, a marked inhibition of PTH-stimulated bone resorption was still observed after 96 h in the continued presence of CGRP.CGRP 10-6-10-8 M) also inhibited resorption stimulated by prostaglandin and 1,25-dihydroxyvitamin D3 in a dose-dependent manner, but had no significant effect on basal bone resorption. In conclusion, these data show that hCGRP inhibits hormone-stimulated bone resorption in vitro. Although it it less potent than calcitonin in the rat, CGRP has been shown to have potency comparable to that of calcitonin in other species, and therefore, a role for CGRP as a therapeutic agent in states of increased bone resorption cannot be ruled out.