Arai M, Assil I Q, Abou-Samra A B
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Endocrinology. 2001 Jan;142(1):446-54. doi: 10.1210/endo.142.1.7879.
The present study reports the isolation of three complementary DNA (cDNA) clones encoding distinct subtypes of CRF receptors from the diploid catfish (cf) species, Ameiurus nebulosus. The first clone encodes a 446-amino acid protein (cfCRF-R1) that is highly homologous to mouse (m) CRF-R1 (93% identical). The cfCRF-R1 messenger RNA is highly expressed in the brain, and its distribution pattern correlates well with that of mammalian CRF-R1, except for weak expression in the pituitary. When transiently expressed in COS-7 cells, cfCRF-R1 bound CRF, urotensin I, and sauvagine with similar affinities. The second full-length cDNA, which was cloned from catfish heart, encodes a 406-amino acid protein that showed homology to murine CRF-R2 (88%) and when expressed in COS-7 cells preferentially bound sauvagine. The highest level of cfCRF-R2 expression was observed in the heart. The third full-length cDNA clone, which encodes a 428-amino acid protein, is structurally closer to cfCRF-R1 (85%) than to cfCRF-R2 (80%). This novel CRF receptor (cfCRF-R3) bound CRF with a 5-fold higher affinity than urotensin I and sauvagine and was expressed in the pituitary gland, urophysis, and brain. The presence of three different CRF receptors, each with distinct tissue distribution and ligand binding properties, suggests a complex CRF/urotensin I system.
本研究报告了从二倍体鲶鱼物种美洲拟鲇中分离出三个编码促肾上腺皮质激素释放因子（CRF）受体不同亚型的互补DNA（cDNA）克隆。第一个克隆编码一种446个氨基酸的蛋白质（cfCRF-R1），它与小鼠（m）CRF-R1高度同源（93%相同）。cfCRF-R1信使核糖核酸在脑中高度表达，其分布模式与哺乳动物CRF-R1的分布模式密切相关，只是在垂体中的表达较弱。当在COS-7细胞中瞬时表达时，cfCRF-R1以相似的亲和力结合CRF、尾加压素I和蛙皮素。从鲶鱼心脏克隆的第二个全长cDNA编码一种406个氨基酸的蛋白质，它与小鼠CRF-R2显示出同源性（88%），并且在COS-7细胞中表达时优先结合蛙皮素。cfCRF-R2的最高表达水平在心脏中观察到。第三个全长cDNA克隆编码一种428个氨基酸的蛋白质，在结构上与cfCRF-R1（85%）的亲缘关系比与cfCRF-R2（80%）更近。这种新的CRF受体（cfCRF-R3）结合CRF的亲和力比尾加压素I和蛙皮素高5倍，并且在垂体、尾垂体和脑中表达。三种不同的CRF受体的存在，每种受体都具有独特的组织分布和配体结合特性，提示存在一个复杂的CRF/尾加压素I系统。
