Biochemical, Anatomical, and Pharmacological Characterization of Calcitonin-Type Neuropeptides in Starfish: Discovery of an Ancient Role as Muscle Relaxants.
Biochemical, Anatomical, and Pharmacological Characterization of Calcitonin-Type Neuropeptides in Starfish: Discovery of an Ancient Role as Muscle Relaxants.
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DOI：
10.3389/fnins.2018.00382
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发表时间：
2018
影响因子：
4.3
通讯作者：
Elphick MR
中科院分区：
文献类型：
--
作者：
Cai W;Kim CH;Go HJ;Egertová M;Zampronio CG;Jones AM;Park NG;Elphick MR
降钙素 (CT) 是一种由甲状腺释放的肽激素，可调节哺乳动物的血液 Ca2+ 水平。 CT基因是选择性剪接的，一个转录本编码CT，另一个转录本编码CT样神经肽降钙素基因相关肽（α-CGRP），这是一种强大的血管扩张剂。脊椎动物中其他与 CT 相关的肽包括肾上腺髓质素、胰淀素和 intermedin，它们也可作为平滑肌松弛剂。 CT 型肽的进化起源可追溯到原口动物和后口动物的两侧对称动物共同祖先，并且 CT 样肽 (DH31) 已被鉴定为某些昆虫物种的利尿激素。然而，人们对 CT 型肽在其他无脊椎动物中的生理作用知之甚少。在这里，我们表征了后口无脊椎动物——海星 Asterias rubens（棘皮动物门）中的 CT 型神经肽。对 CT 型前体 cDNA (ArCTP) 进行了测序，并使用质谱法确认了源自 ArCTP 的肽 (ArCT) 的预测结构。分别使用原位杂交和免疫组织化学研究了 ArCTP mRNA 和 ArCT 肽的分布，揭示了神经系统、消化系统和肌肉器官（包括顶肌和管脚）中的染色细胞/过程。对合成 ArCT 对心尖肌和管足体外制备物的影响的研究表明，它起到松弛剂的作用，引起乙酰胆碱诱导的收缩的剂量依赖性逆转。此外，另一种海星物种 Patiria pectinifera 的整体动物提取物中存在的肌肉松弛剂被鉴定为 ArCT 的直系同源物，并命名为 PpCT。与 A. rubens 中 ArCTP 的表达模式一致，RT-qPCR 显示，在 P. pectinifera 中，PpCT 前体转录物在桡神经索中比在分析的其他组织/器官中更丰富。总之，我们的研究结果表明，CT 相关肽作为脊椎动物肌肉松弛剂的生理作用可能反映了 CT 型神经肽在进化上的古老作用，这种作用可以追溯到后口动物的共同祖先。
Calcitonin (CT) is a peptide hormone released by the thyroid gland that regulates blood Ca2+ levels in mammals. The CT gene is alternatively spliced, with one transcript encoding CT and another transcript encoding the CT-like neuropeptide calcitonin-gene related peptide (α-CGRP), which is a powerful vasodilator. Other CT-related peptides in vertebrates include adrenomedullin, amylin, and intermedin, which also act as smooth muscle relaxants. The evolutionary origin of CT-type peptides has been traced to the bilaterian common ancestor of protostomes and deuterostomes and a CT-like peptide (DH31) has been identified as a diuretic hormone in some insect species. However, little is known about the physiological roles of CT-type peptides in other invertebrates. Here we characterized a CT-type neuropeptide in a deuterostomian invertebrate—the starfish Asterias rubens (Phylum Echinodermata). A CT-type precursor cDNA (ArCTP) was sequenced and the predicted structure of the peptide (ArCT) derived from ArCTP was confirmed using mass spectrometry. The distribution of ArCTP mRNA and the ArCT peptide was investigated using in situ hybridization and immunohistochemistry, respectively, revealing stained cells/processes in the nervous system, digestive system, and muscular organs, including the apical muscle and tube feet. Investigation of the effects of synthetic ArCT on in vitro preparations of the apical muscle and tube feet revealed that it acts as a relaxant, causing dose-dependent reversal of acetylcholine-induced contraction. Furthermore, a muscle relaxant present in whole-animal extracts of another starfish species, Patiria pectinifera, was identified as an ortholog of ArCT and named PpCT. Consistent with the expression pattern of ArCTP in A. rubens, RT-qPCR revealed that in P. pectinifera the PpCT precursor transcript is more abundant in the radial nerve cords than in other tissues/organs analyzed. In conclusion, our findings indicate that the physiological action of CT-related peptides as muscle relaxants in vertebrates may reflect an evolutionarily ancient role of CT-type neuropeptides that can be traced back to the common ancestor of deuterostomes.
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影响因子：
2.7
作者：
Brugge, Victoria Te;Ianowski, Juan P.;Orchard, Ian
通讯作者：
Orchard, Ian
DOI：
10.1073/pnas.0603459103
发表时间：
2006-09-19
影响因子：
11.1
作者：
Kim, Young-Joon;Zitnan, Dusan;Adams, Michael E.
通讯作者：
Adams, Michael E.
鉴定出充当肌肉松弛剂的新型海星神经肽。
影响因子：
4.7
作者：
Kim CH;Kim EJ;Go HJ;Oh HY;Lin M;Elphick MR;Park NG
通讯作者：
Park NG
DOI：
10.1073/pnas.84.23.8628
发表时间：
1987-12-01
影响因子：
11.1
作者：
COOPER, GJS;WILLIS, AC;REID, KBM
通讯作者：
REID, KBM
影响因子：
4.4
作者：
Conzelmann M;Williams EA;Krug K;Franz-Wachtel M;Macek B;Jékely G
通讯作者：
Jékely G