CALCITONIN-GENE-RELATED PEPTIDE (CGRP) IN THE DEVELOPING MOUSE LIMB
CALCITONIN-GENE-RELATED PEPTIDE (CGRP) IN THE DEVELOPING MOUSE LIMB
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DOI：
10.1080/07435809509030488
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发表时间：
1995-01-01
影响因子：
2.1
通讯作者：
BALKAN, W
中科院分区：
文献类型：
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作者：
BIDEGAIN, M;ROOS, BA;BALKAN, W
神经肽的促有丝分裂作用及其在发育组织中的定位表明这些肽在妊娠期间发挥重要作用。我们研究了神经肽降钙素基因相关肽（CGRP）在发育中的小鼠肢芽，一个很好的模型系统研究肌肉骨骼发育的表达和行动。CGRP免疫反应性（CGRP-IR）在妊娠第16.5天（E 16.5）在发育中的肢体中首次检测到，并且仅限于血管周围的神经纤维，发育中的肌肉内或靠近发育中的软骨骨骼。虽然CGRP免疫反应直到E16.5才被观察到，但肢芽早在E11.5就对CGRP有反应。在暴露于CGRP（10（-8）至10（-7）M）的5分钟内，观察到环AMP（cAMP）水平增加2-3倍。这种CGRP诱导的cAMP增加通过加入人CGRP（8-37）（一种CGRP受体拮抗剂）而消除。这一结果表明，对cAMP的影响是通过CGRP与CORP受体的相互作用介导的。我们的研究结果表明，小鼠肢体CGRP时，他们主要是由未分化的间充质和CGRP-IR出现在发展的后期阶段与软骨和肌肉分化。
The mitogenic effects of neuropeptides and their localization to developing tissues suggest an important role for these peptides during gestation. We examined the expression and action of the neuropeptide calcitonin gene-related peptide (CGRP) in the developing mouse limb bud, an excellent model system for studying musculoskeletal development. CGRP immunoreactivity (CGRP-ir) was first detected in the developing limb at day 16.5 of gestation (E 16.5) and was limited to nerve fibers surrounding blood vessels, within the developing muscle or in close proximity to the developing cartilaginous skeleton. Although CGRP-ir was not observed until E 16.5, limb buds were responsive to CGRP as early as E 11.5. Within 5 min of exposure to CGRP (10(-8) to 10(-7) M) a 2-3-fold increase in cyclic AMP (cAMP) levels was observed. This CGRP-induced increase in cAMP was abolished by the addition of human CGRP(8-37), a CGRP receptor antagonist. This result suggests that the effect on cAMP was mediated by the interaction of CGRP with CORP receptors. Our findings indicate that mouse limbs are responsive to CGRP when they are composed of primarily undifferentiated mesenchyme and that CGRP-ir appears at a later stage of development in association with cartilage and muscle differentiation.