Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart.
Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart.
复制标题
DOI：
10.1210/mend.9.5.7565810
复制
发表时间：
1995-05
影响因子：
--
通讯作者：
Peter Stenzel;R. A. Kesterson;Wendy Yeung;R. Cone;Marvin B. Rittenberg;M. Stenzel-Poore
中科院分区：
文献类型：
--
作者：
Peter Stenzel;R. A. Kesterson;Wendy Yeung;R. Cone;Marvin B. Rittenberg;M. Stenzel-Poore
促肾上腺皮质激素释放激素（CRH）是应激反应的主要调节因子。CRH通过位于垂体促肾上腺皮质激素上的特定CRH受体刺激ACTH的产生。除了垂体和中枢神经系统的影响，CRH的外周影响已被观察到涉及免疫和心血管系统。在一些外周器官的特异性CRH结合研究以及功能研究表明外周CRH受体的存在。虽然最近发现了垂体/脑CRH受体，但在观察到CRH效应的外周部位，其表达水平非常低。我们在这里报告了一种在心脏中高度表达的新型小鼠CRH受体的鉴定。新克隆的CRH受体cDNA （CRH- r2）从小鼠心脏cDNA文库中分离得到，编码一个含有7个假定的G蛋白偶联受体跨膜结构域的430个氨基酸的蛋白。CRH- r2与先前鉴定的小鼠垂体CRH受体69%相同，由一个不同的基因编码。除了在心脏中高水平表达外，在脑和肺中也观察到弱表达。利用转染CRH- r2的细胞进行的功能研究表明，CRH和CRH相关的两栖动物肽sauvagine与CRH- r2高亲和力结合，并刺激细胞内cAMP的积累。（摘要删节250字）
Corticotropin-releasing hormone (CRH) is the principal regulator of the stress response. CRH stimulates production of ACTH via specific CRH receptors located on pituitary corticotropes. In addition to pituitary and central nervous system effects, peripheral effects of CRH have been observed involving the immune and cardiovascular systems. Specific CRH binding studies in several peripheral organs, as well as functional studies, have implied the existence of peripheral CRH receptors. Although a pituitary/brain CRH receptor has recently been identified, it is expressed at very low levels in peripheral sites where CRH effects have been observed. We report here the identification of a novel murine CRH receptor that is highly expressed in the heart. The newly cloned CRH receptor cDNA (CRH-R2) was isolated from a mouse heart cDNA library and encodes a 430-amino acid protein containing seven putative transmembrane domains characteristic of G protein-coupled receptors. CRH-R2 is 69% identical with the previously identified murine pituitary CRH receptor and is encoded by a distinct gene. In addition to a high level of expression in the heart, weak expression was also observed in the brain and lungs. Functional studies using CRH-R2-transfected cells indicate that CRH and the CRH-related amphibian peptide, sauvagine, bind with high affinity to CRH-R2 and stimulate intracellular accumulation of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)