Zaidi M, Chambers T J, Bevis P J, Beacham J L, Gaines Das R E, MacIntyre I
Department of Chemical Pathology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Q J Exp Physiol. 1988 Jul;73(4):471-85. doi: 10.1113/expphysiol.1988.sp003168.
The calcitonin-calcitonin gene-related peptide (CGRP) gene complex encodes a family of novel peptides--calcitonin, CGRP and katacalcin. Whereas calcitonin is a circulating hormone involved in skeletal maintenance, the physiological function of CGRP still remains unclear. In the present study we have compared the biological activity of CGRP with that of calcitonin using three experimental systems. We have demonstrated that both peptides inhibit bone resorption by active rat osteoclasts and thus lower plasma calcium when injected into young rats. In both respects the CGRP homologues (rat, human alpha and human beta) were found to be 100- to 1000-fold less potent than human calcitonin. The effects of the CGRP peptides and calcitonin were only additive. Human CGRP (alpha) also caused a marked dose-dependent elevation of bone cyclic AMP levels in mice, somewhat like calcitonin. Though from our studies it would seem reasonably clear that CGRP is weakly agonistic for the calcitonin receptor on the osteoclast to produce effects on bone resorption and plasma calcium, it is still unclear whether the elevation of bone cyclic AMP simply represents an osteoclastic effect or an additional, more important, effect on osteoblasts. It is highly unlikely that CGRP may exert systemic effects on bone. Nevertheless, the peptide may be an important local regulator of bone cell function.
降钙素-降钙素基因相关肽（CGRP）基因复合体编码一类新的肽——降钙素、CGRP和katacalcin。降钙素是一种参与骨骼维持的循环激素，而CGRP的生理功能仍不清楚。在本研究中，我们使用三个实验系统比较了CGRP和降钙素的生物活性。我们证明，当注射到幼鼠体内时，这两种肽都能抑制活跃的大鼠破骨细胞的骨吸收，从而降低血浆钙水平。在这两个方面，发现CGRP同源物（大鼠、人α和人β）的效力比人降钙素低100至1000倍。CGRP肽和降钙素的作用只是相加的。人CGRP（α）也能使小鼠骨中环磷酸腺苷（cAMP）水平显著升高，这有点像降钙素。尽管从我们的研究来看，似乎相当清楚的是，CGRP对破骨细胞上的降钙素受体具有弱激动作用，从而对骨吸收和血浆钙产生影响，但骨cAMP水平的升高仅仅是破骨细胞的作用，还是对成骨细胞的另一种更重要的作用，仍不清楚。CGRP极不可能对骨骼产生全身作用。然而，该肽可能是骨细胞功能的重要局部调节因子。
