G 蛋白偶联受体的非孤儿化。
G protein-coupled receptor deorphanizations.
机构信息
Department of Pharmacology, University of California, Irvine, Irvine, California 92617, USA.
出版信息
Annu Rev Pharmacol Toxicol. 2013;53:127-46. doi: 10.1146/annurev-pharmtox-010611-134548. Epub 2012 Sep 28.
Abstract
G protein-coupled receptors (GPCRs) are major regulators of intercellular interactions. They initiate these actions by being activated by a wide variety of natural ligands. Historically, ligands were discovered first, but the advent of molecular biology reversed this trend. Most GPCRs are identified on the basis of their DNA sequences and thus are initially unmatched to known natural ligands. They are termed orphan GPCRs. Discovering their ligands-i.e., "deorphanizing" the GPCRs-gave birth to the field of reverse pharmacology. This review discusses the present status of GPCR deorphanization, presents a few examples of successes and surprises, and highlights difficulties encountered in these efforts.
摘要
G 蛋白偶联受体（GPCRs）是细胞间相互作用的主要调节剂。它们通过被各种天然配体激活而引发这些作用。历史上，首先发现了配体，但分子生物学的出现扭转了这一趋势。大多数 GPCR 是根据它们的 DNA 序列来识别的，因此最初与已知的天然配体不匹配。它们被称为孤儿 GPCR。发现它们的配体，即“去孤儿化”GPCR，催生了反向药理学领域。这篇综述讨论了 GPCR 去孤儿化的现状，介绍了一些成功和惊喜的例子，并强调了在这些努力中遇到的困难。
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