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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nishina, Kazuya Sakai, Takafumi Koyama, Makoto Hayashi, Yujiro Mondal, Anupom Nishigaki, Koichi Sakata, Ichiro Miura, Kenju Yoshida, Sayaka Nemoto, Naoto Ueno, Shingo |
| Description | Author Affiliation: Ueno S ( Department of Regulation Biology, Faculty of Science, Saitama University, Sakura-ku, Saitama 338-8570, Japan.); |
| Abstract | G protein-coupled receptors (GPCRs) are major drug targets, and their ligands are currently being explored and developed by many pharmaceutical companies and independent researchers. Class A (rhodopsin-like) GPCRs compose a predominant GPCR family; therefore, class A GPCR ligands are in demand. Growth hormone secretagogue receptor (GHS-R) is a class A GPCR that stimulates food intake by binding to its peptide ligand, ghrelin. Therefore, antagonists of GHS-R are expected to exert antiobesity function. In this article, we describe the use of cDNA display to screen for successfully and identify an antagonistic peptide of GHS-R. The antagonistic peptide inhibited the ghrelin-induced increase in intracellular $Ca^{2+}$ in vitro $(IC_{50} = approximately 10 μM)$ and repressed the contraction of isolated animal stomach in response to ghrelin. Furthermore, peripheral administration of the peptide inhibited the food intake of mice. This work provides new insight into the development of antiobesity drugs and describes a method for the discovery of unique peptide ligands for class A GPCRs. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 28 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA, Complementary Metabolism Receptors, Ghrelin Animals Anti-Obesity Agents Pharmacology CHO Cells Calcium Chemistry Cricetinae Cricetulus Dose-Response Relationship, Drug Gene Library Ghrelin In Vitro Techniques Inhibitory Concentration 50 Ligands Mice Models, Biological Peptides Polymerase Chain Reaction RNA, Messenger Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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