Comparison of the effects of calcitonin gene-related peptide and amylin on osteoblasts
Comparison of the effects of calcitonin gene-related peptide and amylin on osteoblasts
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DOI：
10.1359/jbmr.1999.14.8.1302
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发表时间：
1999-08-01
影响因子：
6.2
通讯作者：
Reid, IR
中科院分区：
文献类型：
--
作者：
Cornish, J;Callon, KE;Reid, IR
降钙素基因相关肽（CGRP）和amylin是同源的37氨基酸肽，已被证明具有合成代谢作用。目前尚不清楚这些作用是否由一种共同的受体介导，也不知道哪种配体更有效。这些问题本研究使用文化的胎鼠成骨细胞,CGRP怎样增加细胞数量当出现在浓度大于或等于10 (9)M,但10(8)米CGRP怎样被要求刺激胸苷和苯丙氨酸掺入,糊精是有效的在这些指数以100倍低浓度,和它的最大影响是两倍大的CGRP怎样,ED50的糊精和CGRP怎样的影响细胞数量10(-12)米和10 M (-10),分别。在这些指标上，肽的最大剂量之间不存在可加性。特异性受体阻滞剂对这些肽对细胞数量的最大刺激作用也进行了研究。CGRP受体阻滞剂CGRP-(8-37)在阻滞剂浓度大于或等于10(-9)m时完全阻断了CGRP的作用。当阻滞剂浓度低至10(-11)M时，完全阻断CGRP的作用。CGRP-(8-37)的K-I为2 × 10(-10) M, amylin-(8-37)的K-I为7 × 10(-12) M。在研究最大剂量阻断amylin的反向实验中，amylin-(8-37) 10(-10) M是有效的（K-I 1 × 10(-10) M），而CGRP-(8-37)的100倍浓度才能达到相同的效果（K-I 6 × 10(-9) M）。由此可见，胰淀粉酶和CGRP可能通过一种共同的受体来刺激成骨细胞生长，而这种受体对胰淀粉酶的亲和力高于对CGRP的亲和力。
Calcitonin gene-related peptide (CGRP) and amylin are homologous 37-amino-acid peptides which have been demonstrated to have anabolic effects on bane. It is not clear whether these effects are mediated by a common receptor, nor is it known which ligand is the more potent. These questions are addressed in the present study using cultures of fetal rat osteoblasts, CGRP increased cell number when present in a concentration greater than or equal to 10(-9) M, but 10(-8) M CGRP was required to stimulate thymidine and phenylalanine incorporation, Amylin was effective on these indices at 100-fold lower concentrations, and its maximal effects were about twice as great as those of CGRP, ED50's for the effects of amylin and CGRP on cell number were 10(-12) M and 10(-10) M, respectively. There was no additivity between maximal doses of the peptides on these indices. The effects of specific receptor blockers on the maximal stimulation of cell number by these peptides were also studied, The CGRP receptor-blocker, CGRP-(8-37), completely blocked the effect of CGRP at blocker concentrations greater than or equal to 10(-9) M. In contrast, the amylin receptor blocker, amylin-(8-37), completely blocked the effects of CGRP when the blocker was present in concentrations as low as 10(-11) M. The K-I of CGRP-(8-37) was 2 x 10(-10) M and that of amylin-(8-37) was 7 x 10(-12) M. In converse experiments studying the blockade of maximal doses of amylin, amylin-(8-37) 10(-10) M was effective (K-I 1 x 10(-10) M), whereas a 100-fold greater concentration of CGRP-(8-37) was necessary to achieve the same effect (K-I 6 x 10(-9) M). It is concluded that amylin and CGRP probably act through a common receptor to stimulate osteoblast growth, and that this receptor has a higher affinity for amylin than for CGRP.