THE PHARMACOLOGY AND DISTRIBUTION OF HUMAN 5-HYDROXYTRYPTAMINE(2B) (5-HT2B) RECEPTOR GENE-PRODUCTS - COMPARISON WITH 5-HT2A AND 5-HT2C RECEPTORS
THE PHARMACOLOGY AND DISTRIBUTION OF HUMAN 5-HYDROXYTRYPTAMINE(2B) (5-HT2B) RECEPTOR GENE-PRODUCTS - COMPARISON WITH 5-HT2A AND 5-HT2C RECEPTORS
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DOI：
10.1111/j.1476-5381.1995.tb14977.x
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发表时间：
1995-06-01
影响因子：
7.3
通讯作者：
EGLEN, RM
中科院分区：
文献类型：
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作者：
BONHAUS, DW;BACH, C;EGLEN, RM
1从人肝、肾和胰腺中分离人5-HT 2B受体的全长克隆。克隆的人5-HT 2B受体具有高度的同源性2. PCR扩增用于确定人5-HT 2B受体mRNA的组织分布，编码5-HT 2B受体的mRNA在人肝脏和肾脏中以最大丰度表达，在大脑皮层、鲸脑、胰腺和脾脏。在心脏中未检测到表达。3北方印迹分析证实在胰腺、肝脏和肾脏中存在5-HT 2B受体mRNA（2.4 kB大小的条带）。在肝脏和肾脏中检测到额外的3.2kB大小的杂交条带。这增加了受体剪接变体或存在其他同源受体的可能性。4人5-HT 2B受体在Cos-7细胞中表达，并将其配体结合特征与类似表达的人5-HT 2A和5-HT 2C受体进行比较。人5-HT 2B受体（5-HT >利坦色林> SB 204741 >螺哌隆）的配体特异性不同于人5-HT 2A（利坦色林>螺哌隆> 5-HT > SB 204741）和5-HT 2C（利坦色林> 5-HT >螺哌隆= SB 204741）受体。基于对酮色林的较高亲和力和对育亨宾的较低亲和力，人5-HT 2B受体似乎也不同于大鼠5-HT 2B受体。5这些发现证实了人5-HT 2B受体的序列，并证明该受体具有广泛的组织分布。此外，这些数据表明，有不同物种的受体同源物之间的配体亲和力的差异。最后，在肝脏和肾脏的北方印迹上发现两个不同的条带，这增加了这些组织内5-HT 2B受体的剪接变体或亚型的可能性。
1 Full length clones of the human 5-HT2B receptor were isolated from human liver, kidney and pancreas. The cloned human 5-HT2B receptors had a high degree of homology (similar to 80%) with the rat and mouse 5-HT2B receptors.2 PCR amplification was used to determine the tissue distribution of human 5-HT2B receptor mRNA, mRNA encoding the 5-HT2B receptor was expressed with greatest abundance in human liver and kidney, Lower levels of expression were detected in cerebral cortex, whale brain, pancreas and spleen. Expression was not detected in heart.3 Northern blot analysis confirmed the presence of 5-HT2B receptor mRNA (a 2.4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized band of hybridization was detected in liver and kidney. This raises the possibility of a splice variant of the receptor or the presence of an additional homologous receptor.4 The human 5-HT2B receptor was expressed in Cos-7 cells and its ligand binding characteristics were compared to similarly expressed human 5-HT2A, and 5-HT2C receptors. The ligand specificity of the human 5-HT2B receptor (5-HT > ritanserin > SB 204741 > spiperone) was distinct from that of the human 5-HT2A (ritanserin > spiperone > 5-HT > SB 204741) and 5-HT2C (ritanserin > 5-HT > spiperone = SB 204741) receptors. On the basis of a higher affinity for ketanserin and a lower affinity for yohimbine the human 5-HT2B receptor also appeared to differ from the rat 5-HT2B receptor.5 These findings confirm the sequence of the human 5-HT2B receptor and they demonstrate that the receptor has a widespread tissue distribution. In addition, these data suggest that there are differences in ligand affinities between different species homologues of the receptor. Finally, the finding of two distinct bands on the Northern blots of liver and kidney raises the possibility of splice variants or subtypes of 5-HT2B receptors, within these tissues.