Conlon J M
Regulatory Peptide Center, Department of Biomedical Sciences, Creighton University Medical School, 68178-0405, Omaha NE, USA.
Regul Pept. 2000 Sep 25;93(1-3):3-12. doi: 10.1016/s0167-0115(00)00172-5.
During the past 20 years, several bioactive peptides have been identified in teleost fishes that subsequently have been shown to play important regulatory roles in mammalian physiology. The urophysis, corpuscles of Stannius and Brockmann body are anatomical structures particular to fish that have no obvious counterpart in mammals. Extracts and/or cDNA libraries prepared from these tissues have been used to identify for the first time urotensin II (U-II), urotensin-I (U-I), stanniocalcin and glucagon-like peptide-1 (GLP-1). Although U-II and U-I were originally regarded as exclusively the products of the teleost urophysis, the peptides have a wide phylogenetic distribution across the vertebrate lineage, including mammals. U-II is localized to motor neurones in the human spinal cord and is a potent vasoconstrictor that may be implicated in the pathogenesis of heart failure. The human ortholog of urotensin-I is urocortin which is synthesized in selected regions of the brain and is the endogenous ligand for the CRF type 2 receptor. Urocortin is believed to important in mediating the effects of stress on appetite. Stanniocalcin is involved in maintaining calcium and phosphate homeostasis in teleost fish. An ortholog of stanniocalcin has a widespread distribution in mammalian tissues and is postulated to regulate renal phosphate excretion and to protect neurons against damage during cerebral ischemia. The biological actions and therapeutic potential of GLP-1 in humans are now fully appreciated but the peptide was first identified as a domain in a preproglucagon cDNA prepared from anglerfish Brockmann bodies. In contrast to mammalian preproglucagons, GLP-1 is present in anglerfish preproglucagon as the bioactive, truncated sequence [corresponding to human GLP-1(7-37)] rather than the inactive, N-terminally extended form [corresponding to GLP-1(1-37)]. Failure to appreciate the significance of this fact retarded progress in the field for several years.
在过去20年里，硬骨鱼中已鉴定出几种生物活性肽，随后发现它们在哺乳动物生理学中发挥重要调节作用。尾垂体、斯坦尼斯小体和布罗克曼体是鱼类特有的解剖结构，在哺乳动物中没有明显的对应物。从这些组织制备的提取物和/或cDNA文库首次用于鉴定尾加压素II（U-II）、尾加压素-I（U-I）、鲽鱼降钙素和胰高血糖素样肽-1（GLP-1）。尽管U-II和U-I最初被认为仅是硬骨鱼尾垂体的产物，但这些肽在整个脊椎动物谱系中具有广泛的系统发育分布，包括哺乳动物。U-II定位于人类脊髓中的运动神经元，是一种强效血管收缩剂，可能与心力衰竭的发病机制有关。尾加压素-I的人类同源物是尿皮质素，它在大脑的特定区域合成，是促肾上腺皮质激素释放因子2型受体的内源性配体。尿皮质素被认为在介导应激对食欲的影响方面很重要。鲽鱼降钙素参与维持硬骨鱼的钙和磷稳态。鲽鱼降钙素的一个同源物在哺乳动物组织中广泛分布，据推测可调节肾脏磷酸盐排泄，并在脑缺血期间保护神经元免受损伤。GLP-1在人类中的生物学作用和治疗潜力现在已得到充分认识，但该肽最初是在从安康鱼布罗克曼体制备的前胰高血糖素原cDNA中作为一个结构域被鉴定出来的。与哺乳动物的前胰高血糖素原不同，GLP-1在安康鱼前胰高血糖素原中以生物活性截短序列[对应于人类GLP-1(7-37)]而非无活性的N端延伸形式[对应于GLP-1(1-37)]存在。未能认识到这一事实的重要性阻碍了该领域数年的进展。
