MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF A BRAIN-SPECIFIC SOMATOSTATIN RECEPTOR
MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF A BRAIN-SPECIFIC SOMATOSTATIN RECEPTOR
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DOI：
10.1073/pnas.89.23.11151
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发表时间：
1992-12-01
影响因子：
11.1
通讯作者：
BERELOWITZ, M
中科院分区：
文献类型：
--
作者：
BRUNO, JF;XU, Y;BERELOWITZ, M
采用PCR和常规文库筛选的方法从大鼠基因组文库中克隆了脑特异性生长抑素受体rSSTR-4。推导的氨基酸序列编码384个氨基酸的蛋白质，并显示与G蛋白受体超家族成员的结构和序列同源性。rSSTR-4与生长抑素受体SSTR-1和SSTR-2的氨基酸序列分别有60%和48%的同源性。在COS-1细胞中瞬时表达的受体的结合特性的竞争曲线分析显示，生长抑素14比生长抑素28具有更高的表观亲和力。相反，生长抑素类似物SMS 201-995、IM 4-28和MK-678不能取代转染细胞中的特异性结合。这些特征类似于先前描述的脑特异性生长抑素受体亚型的药理学结合特性。对rSSTR-4的mRNA的组织分布的检查显示，表达限于各种脑区域，在皮质和海马中表达水平最高。因此，基于该受体的药理学和组织定位，我们得出结论，rSSTR-4代表脑特异性生长抑素受体。
The PCR and conventional library screening were used to clone the brain-specific somatostatin receptor rSSTR-4 from a rat genomic library. The deduced amino acid sequence encodes a protein of 384 amino acids and displays structural and sequence homologies with members of the G protein-receptor superfamily. The amino acid sequence of rSSTR-4 is 60% and 48% identical to that of somatostatin receptors SSTR-1 and SSTR-2, respectively, two recently cloned subtypes. Competition curve analysis of the binding properties of the receptor transiently expressed in COS-1 cells revealed a higher apparent affinity for somatostatin 14 than for somatostatin 28. In contrast, the somatostatin analogs SMS 201-995, IM 4-28, and MK-678 failed to displace specific binding in transfected cells. These characteristics resemble the pharmacological binding properties of the previously described brain-specific somatostatin-receptor subtype. Examination of the tissue distribution of mRNA for rSSTR-4 revealed expression limited to various brain regions with highest levels in the cortex and hippocampus. Thus, based on the pharmacology and tissue localization of this receptor, we conclude that rSSTR-4 represents a brain-specific somatostatin receptor.