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恒河猴β2肾上腺素能受体的克隆、测序及表达

Cloning, sequencing, and expression of the rhesus monkey beta 2 adrenergic receptor.

作者信息

Amend A M, Guan X M

机构信息

Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.

出版信息

DNA Cell Biol. 1995 Sep;14(9):753-7. doi: 10.1089/dna.1995.14.753.

DOI:10.1089/dna.1995.14.753
PMID:7669252
Abstract

The beta 2 adrenergic receptor (beta 2AR) plays a key role in the signal transduction mechanism for epinephrine and norepinephrine. The gene for beta 2 adrenergic receptors has been cloned for several species, but has remained undetermined for rhesus monkey. In this study, we report the isolation of the gene encoding the rhesus beta 2AR from both cDNA and genomic DNA sources. Sequence analysis of the gene reveals an intronless open reading frame that encodes a 415-amino-acid protein. The rhesus receptor is highly homologous to that from other species, especially to the human receptor (97% sequence identity). Functional characterization by ligand binding and agonist-mediated cAMP accumulation indicates that the rhesus beta 2 receptor shares a very similar pharmacological profile with the human beta 2 receptor. Therefore, the rhesus monkey represents a valid animal model for developing therapeutic agents targeted at the corresponding human beta 2 receptor.

摘要

β2肾上腺素能受体(β2AR)在肾上腺素和去甲肾上腺素的信号转导机制中起关键作用。β2肾上腺素能受体基因已在多个物种中克隆出来,但恒河猴的该基因仍未确定。在本研究中,我们报告了从cDNA和基因组DNA来源分离出编码恒河猴β2AR的基因。对该基因的序列分析揭示了一个无内含子的开放阅读框,其编码一个415个氨基酸的蛋白质。恒河猴受体与其他物种的受体高度同源,尤其是与人受体(序列同一性为97%)。通过配体结合和激动剂介导的cAMP积累进行的功能表征表明,恒河猴β2受体与人β2受体具有非常相似的药理学特征。因此,恒河猴是开发针对相应人类β2受体的治疗药物的有效动物模型。

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