Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor.
Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor.
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DOI：
10.1210/endo.133.6.8243338
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发表时间：
1993-12
期刊：
影响因子：
4.8
通讯作者：
M. Perrin;Cynthia J. Donaldson;Ruoping Chen;K. Lewis;W. Vale
中科院分区：
文献类型：
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作者：
M. Perrin;Cynthia J. Donaldson;Ruoping Chen;K. Lewis;W. Vale
促肾上腺皮质激素释放因子 (CRF) 是下丘脑-垂体-肾上腺皮质轴的关键神经调节剂，对内分泌、中枢神经和免疫系统也显示出广泛的影响。最近，我们通过表达克隆人库欣促皮质腺瘤的 cDNA 来表征人垂体 CRF 受体，在此报告了通过杂交从大鼠脑 cDNA 文库中克隆的大鼠脑 CRF 受体 (rCRF-R) 的 cDNA 结构。 rCRF-R的序列编码包含7个跨膜结构域的415个氨基酸的蛋白质。 rCRF-R 在氨基酸水平上与人垂体瘤 CRF 受体有 97% 的相同性，仅相差 12 个氨基酸。当在 COSM6 细胞中表达时，rCRF-R 以高亲和力 (Kd = 1.7 (0.8-3.8)nM) 结合 CRF。该受体转导 CRF 刺激的细胞内 cAMP 积累，而该积累可被 CRF 拮抗剂 α helCRF(9-41) 抑制。这些结果表明大脑表达与垂体相似的 CRF 受体。
Corticotropin releasing factor (CRF), a key neuroregulator of the hypothalamic-pituitary-adrenal cortical axis, also displays a broad range of effects on the endocrine, central nervous and immune systems. Having recently characterized the human pituitary CRF receptor by expression cloning of cDNA from a human Cushing's corticotropic adenoma, we report here the structure of the cDNA for a rat brain CRF receptor (rCRF-R) which was cloned by hybridization from a rat brain cDNA library. The sequence of the rCRF-R encodes a 415 amino acid protein comprising seven membrane spanning domains. The rCRF-R is 97% identical at the amino acid level to the human pituitary tumor CRF receptor, differing by only 12 amino acids. When expressed in COSM6 cells, the rCRF-R binds CRF with high affinity (Kd = 1.7 (0.8-3.8)nM). The receptor transduces a CRF stimulated accumulation of intracellular cAMP which is inhibited by the CRF antagonist, alpha helCRF(9-41). These results suggest that the brain expresses a CRF receptor similar to that in the pituitary.