Reyes T M, Lewis K, Perrin M H, Kunitake K S, Vaughan J, Arias C A, Hogenesch J B, Gulyas J, Rivier J, Vale W W, Sawchenko P E
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2843-8. doi: 10.1073/pnas.051626398.
Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)(+) RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1-10 microg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation.
在此，我们描述了一种先前未被鉴定的促肾上腺皮质激素释放因子（CRF）相关神经肽——尿皮质素II（Ucn II）的克隆及初步特性研究。对公共人类基因组数据库进行检索，发现了一个与CRF神经肽家族具有显著序列同源性的区域。通过使用从人类序列推导而来的同源引物，从全脑聚腺苷酸（poly(A)）⁺RNA中分离出一个小鼠cDNA，该cDNA编码一种预测的38个氨基酸的肽，其结构与其他已知的哺乳动物家族成员CRF和Ucn相关。Ucn II选择性地与2型CRF受体（CRF-R2）结合，对CRF-R1没有明显活性。编码Ucn II的转录本在啮齿动物中枢神经系统的离散区域表达，包括下丘脑（室旁核和弓状核）和脑干（蓝斑）中与应激相关的细胞群。向中枢注射1 - 10微克该肽，优先在一个服务于自主神经和神经内分泌调节的核心神经回路中引发激活反应（诱导Fos蛋白表达），但其总体模式并未广泛模仿CRF-R2的分布。在行为方面，中枢给予Ucn II可减弱夜间进食，其时间进程与对CRF的反应不同。然而，与CRF相反，中枢给予Ucn II未能增加总体运动活动。这些发现确定Ucn II是CRF神经肽家族的一个新成员，它在中枢表达并选择性地与CRF-R2结合。初步功能研究表明，Ucn II参与中枢自主神经和食欲控制，但不参与全身性的行为激活。
