期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 53, 2013
卷 53, 期 -, 页码 127-146出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010611-134548
关键词
orphan receptors; neuropeptides; reverse pharmacology; phylogeny; lipid mediators
资金
- NIDA NIH HHS [DA024746, R01 DA024746] Funding Source: Medline
- NIMH NIH HHS [MH60231, R01 MH060231, MH093521, R21 MH093521] Funding Source: Medline
- Novo Nordisk Fonden [NNF12OC1016287] Funding Source: researchfish
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.
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